In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

In my last column, I summarized a lecture given by Jeffrey Swanson, Ph.D., a medical sociologist who studies outcomes with outpatient civil commitment. Several readers posted comments, including a very articulate letter from Evelyn Burton, a patient advocate who is on the Public Policy Committee of the National Alliance on Mental Illness–Maryland (NAMI MD).

Ms. Burton, along with one or two other commenters, believed that I missed the point of "assisted outpatient treatment" (AOT) and did not understand the target population; and I will contend that, with 20 years of experience in four community mental health centers, including Baltimore’s Health Care for the Homeless, I do understand that there are some people who might do better if forced to undergo treatment. I also understand that the consequences of untreated mental illness can be both trying and tragic for the patients and their families.

Because Maryland has not legalized forced outpatient care, I do not have experience with this, and I was struck by the fact that Dr. Swanson felt that much of the benefit of forcing treatment could be explained by the way AOT obligates society to the patient by granting these patients case management services, housing, and access to mental health care – things that society is not obligated to provide for those with severe psychotic disorders who willingly seek care. Done poorly, AOT is often unenforceable and poorly funded, and laws may be written such that the intended target population – the sickest, most psychotic members of society who cycle in and out of hospitals due to their noncompliance – are not clearly identified as those to receive "assisted" treatment.

While we may agree or disagree as to whether AOT is helpful and under what circumstances and whether it benefits those who might otherwise end up on the streets, in jail, or dead, the truth is that states with AOT still have psychotic people living on the streets and eating from the garbage. AOT has not proven to be a panacea for homelessness, suicide, or wasted lives. I realize that to a parent who fears her child might join those ranks, the heartbreak is immense, and the anecdotes about forced treatment offer hope.

I have no doubt that there are times when AOT, together with its attendant services, provides a lifeline. It’s unfortunate – if not disgraceful – that these services are not routinely provided to our sickest members of society. Still, it’s important to make sure that any given patient’s civil rights be considered. I’m also well aware that there are people who believe that a discussion of civil rights has no place in the treatment of psychosis, and there we will need to respectfully disagree.

While Ms. Burton’s heartfelt letter was articulate and compelling, I have to say that I was taken back by one paragraph. I expressed concern that patients do not generally endorse involuntary treatments, and I suggested that we need to look at why the treatments we offer are not palatable to those receiving forced care.

Ms. Burton responded:

"You do not need to waste your time trying to figure out why your treatment is not palatable to this particular group of individuals. NAMI MD families can tell you, you are asking the wrong question. It has nothing to do with palatable services and everything to do with anosognosia."

I was baffled by this. Compliant patients with good insight complain about side effects. If they take antipsychotic medications, they sometimes feel sedated, and they are told of the risks of weight gain, diabetes, and hyperlipidemia, conditions that can decrease both the quality and length of their lives. Sometimes we have little choice and are left to say that we believe the benefit to the patient is worth the trade-off, but with voluntary patients, the ultimate decision is theirs. Sometimes patients talk with their feet. Sometimes they fare better without medications, therapy, and the other treatments we have to offer, and sometimes they fare catastrophically worse. If they always did better, lived fuller, healthier, happier, and longer lives with the treatments we offer, the choice would be simple. Unfortunately, the medications we offer to treat psychosis are not benign.

The idea that "anosognosia," or simply lack of insight, is the pivotal issue, is a difficult one. People with substance abuse disorders, especially alcoholism and cannabis abuse, may insist that their use of these intoxicants is consistent with the societal norms around them and deny that it’s a problem, despite the difficulties it brings to them. And people with major mental illnesses may deny their existence, but still come to appointments and take prescribed medications. Patients can lack insight at one point in time and gain it later. The issue should not be the patient’s insight, because that label may be stamped on anyone who simply disagrees with their diagnosis or treatment recommendations.

The risk of labeling people with anosognosia is that we might cease to see them as humans, that we might write off their resistance to treatment as simply an inability to know what’s best for them, in a way that enables us to close our ears to what may well be their valid concerns. It may become too easy to say that the court order calls for the medications, and changing doses or medications to alter the risks or the side-effect profile is no longer part of the effort. Such a mind-set may lead the psychiatrist to complacence and disregard for the patient’s concerns.

Why take the time to know the patient, to develop rapport, to convince the patient to come to therapy and to try medications on his terms, when a court order might cut all those corners and a nurse can administer an injection? That’s not the targeted group of patients, you say, that’s not whom AOT captures. If we’re not careful – if we feel that addressing the concerns of our patients is simply a "waste of time" because, after all, they have no insight – then we risk losing sight of what needs to be our real goal: helping patients to live the lives they want to live in productive and meaningful ways. Forcing treatment may get one person help at a particular period in time, but it comes with a cost: It leaves some patients afraid to seek voluntary care for fear of what may occur down the line, and it stigmatizes our profession. Finally, it makes us the adversaries of the patients we serve.

It would be easy to read this and think I’m against involuntary outpatient treatment, and that’s not completely true (ah, it’s mostly true). If involuntary treatment is limited to those patients who cycle in and out of hospitals and jails because of noncompliance, who become dangerous when ill, for whom treatment has proven to be effective, and who have failed thoughtful attempts at voluntary care, then forced care with its array of ancillary services and housing provisions may be a reasonable resource, regardless of the patient’s level of insight. Still, I remain interested in making our treatments more palatable to all of our patients – those who are forced into care as well as those who come willingly – and I believe it’s a mistake to see that effort as a waste of anyone’s time.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Just because a dermatologist has photodynamic therapy equipment in the office doesn’t mean it should be applied to every skin condition that comes through the door, Dr. Jerome M. Garden cautioned at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

"Used selectively, I think PDT can be truly worthwhile in some of our patients. But we run into problems when we decide it’s a cure-all for everything. Just because it’s available does not always make it the best choice around," said Dr. Garden, who is director of the Physicians Laser and Dermatology Institute as well as a professor of clinical dermatology and biomedical engineering at Northwestern University in Chicago.

Looking through the literature, it’s quickly apparent that PDT has been used to treat a bewildering array of dermatologic disorders, in most cases with less than stellar results.

"In my practice, I’m using PDT to treat just two things: actinic keratoses and actinic cheilitis, which is a close cousin. Why am I not using it to treat more disease processes? Because it has to be worth it. PDT is not simple to do. It takes a lot of your time and it costs you money. Insurance doesn’t necessarily help you with this. Either the patient’s insurance will reimburse you at an incredibly low rate, where it’s basically costing you money to do it, or you go outside of the insurance – and PDT is an expensive procedure," he noted.

The substantial time expenditure involved in PDT stems from the need to use microdermabrasion or another method of skin preparation to help the topical photosensitizing agent penetrate better. This is followed by an incubation time of 1-3 hours as the photosensitizer finds its target, and then light therapy to create the reactive oxygen species, which kills the targeted cells. The duration of light therapy is source dependent; blue light, for example, must be applied for 15-20 minutes.

PDT has other shortcomings in addition to the cost and time involved. It can be painful and entails several days of down time because of scaling and crusting. Plus, multiple treatment sessions are usually required, the dermatologist continued.

The 2012 American Society for Dermatologic Surgery member survey found that dermatologic surgeons performed roughly 205,000 PDT procedures during the year. The bulk was for actinic keratoses, acne, and rosacea.

"I didn’t even know until I saw this list that anybody treats rosacea with PDT," noted Dr. Garden. "A lot of people out there who are doing PDT use it for many more things than I do. But I’m just telling you what I do."

"I’ve tried it for acne. It helps, but depending on the light source, it can be a painful procedure. There’s a lot of desquamation afterward, and you have to go through it a few times. So you have to have a highly motivated patient – and even then, it doesn’t work all the time," he said.

Dr. Garden cited a Danish split-face study of pulsed-dye laser-assisted PDT vs. pulsed-dye laser therapy alone. Twelve weeks after completing three treatment sessions, the PDT side showed an 80% reduction in inflammatory acne lesions, compared with a 67% drop with pulsed-dye laser, and a 53% decrease in noninflammatory lesions compared to a 42% reduction with laser alone (J. Am. Acad. Dermatol. 2008; 58:387-94).

"Even without the topical photosensitizer, patients did pretty well," he commented.

As for PDT in cutaneous malignancies, Dr. Garden highlighted a recent literature review by dermatologists at the University of South Florida, Tampa, which concluded that the therapy is equivalent or superior to cryosurgery for actinic keratoses. The investigators also deemed PDT suitable for Bowen’s disease lesions provided they are large, widespread, or on difficult to treat areas, as well as for squamous cell carcinomas, but only when surgery is contraindicated. PDT may also provide better cosmetic outcomes than surgery or cryosurgery for superficial basal cell carcinomas (Dermatol. Surg. 2013;39:1733-44).

Dr. Garden called PDT his current first-line treatment for actinic cheilitis.

"I used to use the CO₂ laser exclusively. It works very well, much better than PDT. But when I’d strip off the top layer of skin with the CO₂ laser, patients would end up with an open wound that took a long time to heal. That’s hard for the patient to tolerate. And occasionally we’d see fibrosis of the lip. You don’t see that with PDT, although with PDT you usually need to do two or three treatments, and the area is red and swollen for 2-4 days. I like PDT. It’s my go-to therapy. When it fails, I turn on the CO₂ laser," he said.

In treating actinic keratoses, he reserves PDT for patients with numerous lesions over a large field.

"It does work, but it’s a lot of effort. So if you’re just going after a handful of [actinic keratoses] do you need PDT? Probably not," Dr. Garden said.

Ending on an encouraging note, the dermatologist pointed to the ongoing substantial research commitment to PDT as very promising. Finding more specific photosensitizers is a priority. And ablative fractional laser-assisted delivery of the standard photosensitizer methyl aminolevulinic acid appears to be "an exciting development," in Dr. Garden’s view, although to date the work is limited to animal studies.

Dr. Garden reported having financial relationships with Alma, Candela & Syneron, and Palomar/Cynosure.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Lab mouse

Results of preclinical research point to a possible way of preventing mucositis, graft-vs-host disease, and other disorders associated with epithelial permeability.

Investigators created a mouse model of mucositis and discovered that interleukin-1 (IL-1) beta, a protein secreted by the stressed mucosa, played an important role in the condition.

But inhibiting IL-1 beta alleviated mucositis. So the researchers speculated that targeting IL-1 beta might prevent mucositis in humans.

Naama Kanarek, a doctoral student at Hebrew University Hadassah Medical School in Jerusalem, and her colleagues described this research in PNAS.

The investigators began by generating a mouse model deficient in a gene encoding the enzyme beta-TrCP. They chose this enzyme because it’s a major regulator of inflammatory cascades.

The team found that beta-TrCP deletion in the gut caused mucosal DNA damage in the mice, mimicking the effects of chemotherapy and irradiation. Similar to human patients, a severe mucositis reaction occurred in mice that were genetically engineered to be beta-TrCP-deficient.

Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was IL-1 beta. IL-1 beta opened the gut lining, allowing gut bacteria to penetrate and destroy the gut interior.

To confirm this finding, the researchers treated mice with an antibody neutralizing IL-1 beta prior to deleting beta-TrCP. They found this prevented the onset of mucositis.

Therefore, the team has proposed that IL-1 receptor agonists should be tested as mucositis prophylaxis in humans. An example is anakinra (Kineret), which is used to treat chronic inflammatory conditions, such as rheumatoid arthritis and Crohn’s disease.

The investigators believe such treatments might also be used to prevent graft-vs-host disease, burn injuries, head and neck trauma, and other disorders associated with

epithelial permeability.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Infants who develop leukemia during the first year of life inherit a combination of genetic variations that can make them highly susceptible to the disease, according to a study published in Leukemia.

Results of whole-exome sequencing suggested that infants with leukemia inherited genetic variants from both parents that, by themselves, would not cause leukemia but, in combination, put the infants at high risk of developing the disease.

“We sequenced every single gene and found that infants with leukemia were born with an excess of damaging changes in genes known to be linked to leukemia,” said study author Todd Druley, MD, PhD, of Washington University School of Medicine in St Louis, Missouri.

“For each child, both parents carried a few harmful genetic variations in their DNA, and, just by chance, their child inherited all of these changes.”

However, it’s unlikely that the inherited variations alone cause leukemia, Dr Druley said. The infants likely needed to accumulate a few additional variations.

To uncover these findings, Dr Druley and his colleagues performed whole-exome sequencing in infants with acute myeloid leukemia (AML), infants with acute lymphoblastic leukemia (ALL), and the mothers of these children. The researchers used the process of elimination to determine a father’s contribution to a child’s DNA.

Among the 23 families studied, there was no history of pediatric cancers. As a comparison, the researchers also sequenced the DNA of 25 healthy children.

The team found the average amount of congenital coding variations was higher in infants with leukemia than in their mothers or the control subjects. The average total variants per exome was 1264.4 in infants with ALL, 1112.6 in their mothers, 2549.9 in infants with AML, 1225.0 in their mothers, and 582.8 in healthy controls.

The researchers then decided to home in on variants that were likely to impart a functional effect associated with leukemia. Using the COSMIC database, the team identified 126 ALL-associated genes and 655 AML-associated genes.

They found an average of 12.1 variants per ALL patient in the ALL-associated genes and 163.4 variants per AML patient in the AML-associated genes. There were 6.4 ALL-associated variants in the ALL patients’ mothers, 132.5 AML-associated variants in the AML patients’ mothers, 1.9 ALL variants in controls, and 27.5 AML variants in controls.

To prioritize genes that might be most relevant to infant leukemia, the researchers looked for compound heterozygous genes and the genes that were most commonly variant in all patients.

All of the infants with AML and 50% of the infants with ALL were compound heterozygotes for MLL3.  Sixty-seven percent of AML patients were compound heterozygotes for RYR1 and FLG, and 50% of ALL patients were compound heterozygotes for RBMX.

The most variant (but not necessarily compound heterozygous) AML-associated genes in infants with AML were TTN, MLL3, and FLG. But the ALL-associated genes MDN1, SYNE1, and MLL2 were frequently variable in AML patients as well.

For infants with ALL, MDN1 was the most variable ALL-associated gene. But these infants also had frequent variations in the AML-associated genes TTN, RBMX, and MLL3.

Dr Druley and his colleagues plan to study these variations in more detail to understand how they contribute to infant leukemia development.

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”

Anopheles gambiae mosquito

Credit: CDC

Malaria prevalence maps indicate that, in 2010, nearly 184 million Africans were still living in areas where there is a high risk of contracting malaria, despite a decade of efforts to control the spread of the disease.

The maps showed that 40 African countries experienced reductions in childhood malaria transmission between 2000 and 2010.

Despite this progress, 57% of the population in malaria-endemic countries continued to live in areas of moderate to intense malaria transmission, with infection rates higher than 10%.

These findings are published in The Lancet.

Researchers compiled data from a collection of 26,746 community-based surveys of Plasmodium falciparum prevalence. The surveys covered 3,575,418 person observations from 44 malaria-endemic countries and territories in Africa since 1980.

“Health information systems in many African countries are weak, and it has been difficult to reliably estimate how many people get sick or die of malaria,” said study author Abdisalan Mohamed Noor, PhD, of the Kenya Medical Research Institute-Wellcome Trust Research Programme in Nairobi and the University of Oxford in the UK.

“The population surveys we used in this study are a more reliable indicator for tracking, and we hope our study will help countries assess their progress and adapt their strategies for more effective malaria control.”

Using model-based geostatistics, Dr Noor and his colleagues estimated the proportion of the population, aged 2 to 10 years old, infected with different levels of P falciparum across Africa in 2000 and 2010.

The researchers wanted to evaluate the effects of the Roll Back Malaria Partnership, which was launched in 2000 and resulted in a large increase in investments targeting malaria control.

The team found that the number of people living in high-risk areas, where more than 50% of the population is likely to carry infections, fell from 218.6 million in 2000 to 183.5 million in 2010—a 16% decrease.

But the population living in areas where the risk of infection is considered moderate to high grew from 178.6 million to 280.1 million—a 57% increase.

And the population living in areas where risk is regarded as very low grew from 78.2 million to 128.2 million—a 64% increase.

The researchers also discovered that 10 countries harbor 87% of the population remaining at high risk of malaria transmission. These countries are Guinea, Togo, Mali, Mozambique, Burkina Faso, Ghana, Côte d’Ivoire, Uganda, Nigeria, and the Democratic Republic of Congo.

On the other hand, the team noted that 7 countries have levels of malaria transmission so low that eliminating the disease is a realistic goal. These countries are Cape Verde, Eritrea, South Africa, Ethiopia, Swaziland, Djibouti, and Mayotte.

“The results of our analysis are pause for thought,” said study author Robert Snow, PhD, also of the Kenya Medical Research Institute-Wellcome Trust Research Programme and the University of Oxford.

“On the one hand, it’s a glass half full, with several countries showing significant reductions in malaria transmission. And on the other, it’s a glass half empty, where, despite a decade of massive investment in malaria control, the populations living in several African countries are as likely to be infected with malaria in 2000 as they were 10 years later.”

Chronic lymphocytic leukemia

Researchers believe they’ve discovered how the Bcl-2 protein helps leukemia and lymphoma cells survive anticancer treatment.

The team found that Bcl-2 alters the level of calcium ions in cancer cells, and this promotes the cells’ survival.

The group thinks these findings, published in PNAS, could help spur the development of drugs that effectively inhibit Bcl-2 and produce better outcomes for cancer patients.

“Since 1993, our team has been conducting research on key mechanisms by which the protein Bcl-2 keeps cancer cells alive,” said study author Clark W. Distelhorst, MD, of Case Western Reserve School of Medicine in Cleveland, Ohio.

“Now, for the first time, we have evidence of how Bcl-2 is promoting abnormally long survival of the cancer cells by regulating calcium levels within cells, and [we] will use the discovery and data to deliver therapies designed to attack the Bcl-2 protein and inhibit its impact.”

More than a decade ago, researchers in Dr Distelhorst’s lab discovered that Bcl-2 binds to the inositol 1,4,5-trisphosphate receptor (InsP3R) channel and regulates the release of calcium ions.

In the current study, the team found that when Bcl-2 binds to the InsP3R channel, it initiates a complex feedback mechanism that blocks the release of calcium ions intended to induce cell death. Instead of dying, the cancer cells continue to proliferate.

Specifically, the researchers discovered that Bcl-2 interacts with the Ca2+-activated protein phosphatase calcineurin (CaN) and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a CaN-regulated inhibitor of protein phosphatase 1.

Bcl-2 docks DARPP-32 and CaN on the InsP3R, creating a negative feedback loop that responds to InsP3R-mediated Ca2+ release by inhibiting InsP3R phosphorylation at Ser1755. And this prevents the excessive Ca2+ elevation that induces cell death.

The team theorized that cancer cells overexpressing Bcl-2 may exploit this mechanism to prevent apoptosis. And experiments in chronic lymphocytic leukemia cells appeared to confirm this theory.

The researchers treated the cells with the peptide TAT-IDPDD/AA, which inhibits Bcl-2–InsP3R interaction. This increased P-Ser1755 InsP3R-1 levels and elevated Ca2+, which induced apoptosis.

“We have recognized for decades that cancer cells grow and forget to die,” said Stanton Gerson, MD, director of the Case Comprehensive Cancer Center, who was not involved in this study.

“[N]ow, we understand why. I predict that this work will focus the discovery of new drugs against the Bcl-2-calcium-flow system.”

Chronic lymphocytic leukemia

Researchers believe they’ve discovered how the Bcl-2 protein helps leukemia and lymphoma cells survive anticancer treatment.

The team found that Bcl-2 alters the level of calcium ions in cancer cells, and this promotes the cells’ survival.

The group thinks these findings, published in PNAS, could help spur the development of drugs that effectively inhibit Bcl-2 and produce better outcomes for cancer patients.

“Since 1993, our team has been conducting research on key mechanisms by which the protein Bcl-2 keeps cancer cells alive,” said study author Clark W. Distelhorst, MD, of Case Western Reserve School of Medicine in Cleveland, Ohio.

“Now, for the first time, we have evidence of how Bcl-2 is promoting abnormally long survival of the cancer cells by regulating calcium levels within cells, and [we] will use the discovery and data to deliver therapies designed to attack the Bcl-2 protein and inhibit its impact.”

More than a decade ago, researchers in Dr Distelhorst’s lab discovered that Bcl-2 binds to the inositol 1,4,5-trisphosphate receptor (InsP3R) channel and regulates the release of calcium ions.

In the current study, the team found that when Bcl-2 binds to the InsP3R channel, it initiates a complex feedback mechanism that blocks the release of calcium ions intended to induce cell death. Instead of dying, the cancer cells continue to proliferate.

Specifically, the researchers discovered that Bcl-2 interacts with the Ca2+-activated protein phosphatase calcineurin (CaN) and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a CaN-regulated inhibitor of protein phosphatase 1.

Bcl-2 docks DARPP-32 and CaN on the InsP3R, creating a negative feedback loop that responds to InsP3R-mediated Ca2+ release by inhibiting InsP3R phosphorylation at Ser1755. And this prevents the excessive Ca2+ elevation that induces cell death.

The team theorized that cancer cells overexpressing Bcl-2 may exploit this mechanism to prevent apoptosis. And experiments in chronic lymphocytic leukemia cells appeared to confirm this theory.

The researchers treated the cells with the peptide TAT-IDPDD/AA, which inhibits Bcl-2–InsP3R interaction. This increased P-Ser1755 InsP3R-1 levels and elevated Ca2+, which induced apoptosis.

“We have recognized for decades that cancer cells grow and forget to die,” said Stanton Gerson, MD, director of the Case Comprehensive Cancer Center, who was not involved in this study.

“[N]ow, we understand why. I predict that this work will focus the discovery of new drugs against the Bcl-2-calcium-flow system.”

Chronic lymphocytic leukemia

Researchers believe they’ve discovered how the Bcl-2 protein helps leukemia and lymphoma cells survive anticancer treatment.

The team found that Bcl-2 alters the level of calcium ions in cancer cells, and this promotes the cells’ survival.

The group thinks these findings, published in PNAS, could help spur the development of drugs that effectively inhibit Bcl-2 and produce better outcomes for cancer patients.

“Since 1993, our team has been conducting research on key mechanisms by which the protein Bcl-2 keeps cancer cells alive,” said study author Clark W. Distelhorst, MD, of Case Western Reserve School of Medicine in Cleveland, Ohio.

“Now, for the first time, we have evidence of how Bcl-2 is promoting abnormally long survival of the cancer cells by regulating calcium levels within cells, and [we] will use the discovery and data to deliver therapies designed to attack the Bcl-2 protein and inhibit its impact.”

More than a decade ago, researchers in Dr Distelhorst’s lab discovered that Bcl-2 binds to the inositol 1,4,5-trisphosphate receptor (InsP3R) channel and regulates the release of calcium ions.

In the current study, the team found that when Bcl-2 binds to the InsP3R channel, it initiates a complex feedback mechanism that blocks the release of calcium ions intended to induce cell death. Instead of dying, the cancer cells continue to proliferate.

Specifically, the researchers discovered that Bcl-2 interacts with the Ca2+-activated protein phosphatase calcineurin (CaN) and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a CaN-regulated inhibitor of protein phosphatase 1.

Bcl-2 docks DARPP-32 and CaN on the InsP3R, creating a negative feedback loop that responds to InsP3R-mediated Ca2+ release by inhibiting InsP3R phosphorylation at Ser1755. And this prevents the excessive Ca2+ elevation that induces cell death.

The team theorized that cancer cells overexpressing Bcl-2 may exploit this mechanism to prevent apoptosis. And experiments in chronic lymphocytic leukemia cells appeared to confirm this theory.

The researchers treated the cells with the peptide TAT-IDPDD/AA, which inhibits Bcl-2–InsP3R interaction. This increased P-Ser1755 InsP3R-1 levels and elevated Ca2+, which induced apoptosis.

“We have recognized for decades that cancer cells grow and forget to die,” said Stanton Gerson, MD, director of the Case Comprehensive Cancer Center, who was not involved in this study.

“[N]ow, we understand why. I predict that this work will focus the discovery of new drugs against the Bcl-2-calcium-flow system.”

WAIKOLOA, HAWAII – Our editor, Heidi Splete, catches up with attendees at the Hawaii Dermatology Seminar to find out what they learned at the meeting that they will take back to their practices.

During a coffee break video interview, doctors said they enjoyed presentations on tips to treat fine lines around the eyes and mouth, the link between psoriasis and increased cardiovascular risks, and the "two Cs" of potential leather allergies.

hsplete@frontlinemedcom.com

WAIKOLOA, HAWAII – Our editor, Heidi Splete, catches up with attendees at the Hawaii Dermatology Seminar to find out what they learned at the meeting that they will take back to their practices.

During a coffee break video interview, doctors said they enjoyed presentations on tips to treat fine lines around the eyes and mouth, the link between psoriasis and increased cardiovascular risks, and the "two Cs" of potential leather allergies.

hsplete@frontlinemedcom.com

WAIKOLOA, HAWAII – Our editor, Heidi Splete, catches up with attendees at the Hawaii Dermatology Seminar to find out what they learned at the meeting that they will take back to their practices.

During a coffee break video interview, doctors said they enjoyed presentations on tips to treat fine lines around the eyes and mouth, the link between psoriasis and increased cardiovascular risks, and the "two Cs" of potential leather allergies.

hsplete@frontlinemedcom.com

The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.

Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.

For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.

©Sebastian Kaulitzki/Fotolia.com

The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).

The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.

Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.

Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.

Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.

The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.

Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.

For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.

©Sebastian Kaulitzki/Fotolia.com

The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).

The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.

Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.

Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.

Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.

The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.

Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.

For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.

©Sebastian Kaulitzki/Fotolia.com

The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).

The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.

Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.

Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.

Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.

Background There is often a lack of collaboration between hematological malignancy–bone marrow transplantation (HM-BMT) units and palliative care (PC) services. In this paper, we describe a quality improvement project that sought to close this gap at a tertiary care hospital in Pittsburgh, Pennsylvania, from August 2006 to May 2010.
 

Design and methods Through a needs assessment, didactic lectures, clinical consultation, and the informal presence of PC clinicians, the team created a palliative care service in HM-BMT unit of the Western Pennsylvania Hospital in Pittsburgh. The following data were collected for each consult: referral reason, daily pain assessments, whether or not a “goals of care” conversation took place, and hospice enrollment. Lastly, satisfaction surveys were administered.
 

Results During the program, 392 PC consultations were provided to 256 unique patients. Of these 256 patients, the PC clinicians documented the first goals of care conversations in 67% of patients (n = 172). Of the 278 consults referred for pain, 70% (n = 194) involved reports of unacceptable or very unacceptable pain at baseline. Sixty-six percent (n = 129) of these 194 consults involved reports of pain that was acceptable or very acceptable within 48 hours of consultation. In addition, the hospice referral rate grew from a pre-implementation rate of 5% to 41% (n = 67) of 165 patients who died during the period of program implementation. Lastly, hematological oncologists reported high levels of satisfaction with the program.
 

Limitations The main limitation of this project is that it was a single institution study.
 

Conclusion The successful integration of a PC team into a hematological malignancy unit suggests great potential for positive interdisciplinary collaboration between these two fields.
 

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

Background There is often a lack of collaboration between hematological malignancy–bone marrow transplantation (HM-BMT) units and palliative care (PC) services. In this paper, we describe a quality improvement project that sought to close this gap at a tertiary care hospital in Pittsburgh, Pennsylvania, from August 2006 to May 2010.
 

Design and methods Through a needs assessment, didactic lectures, clinical consultation, and the informal presence of PC clinicians, the team created a palliative care service in HM-BMT unit of the Western Pennsylvania Hospital in Pittsburgh. The following data were collected for each consult: referral reason, daily pain assessments, whether or not a “goals of care” conversation took place, and hospice enrollment. Lastly, satisfaction surveys were administered.
 

Results During the program, 392 PC consultations were provided to 256 unique patients. Of these 256 patients, the PC clinicians documented the first goals of care conversations in 67% of patients (n = 172). Of the 278 consults referred for pain, 70% (n = 194) involved reports of unacceptable or very unacceptable pain at baseline. Sixty-six percent (n = 129) of these 194 consults involved reports of pain that was acceptable or very acceptable within 48 hours of consultation. In addition, the hospice referral rate grew from a pre-implementation rate of 5% to 41% (n = 67) of 165 patients who died during the period of program implementation. Lastly, hematological oncologists reported high levels of satisfaction with the program.
 

Limitations The main limitation of this project is that it was a single institution study.
 

Conclusion The successful integration of a PC team into a hematological malignancy unit suggests great potential for positive interdisciplinary collaboration between these two fields.
 

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

Background There is often a lack of collaboration between hematological malignancy–bone marrow transplantation (HM-BMT) units and palliative care (PC) services. In this paper, we describe a quality improvement project that sought to close this gap at a tertiary care hospital in Pittsburgh, Pennsylvania, from August 2006 to May 2010.
 

Design and methods Through a needs assessment, didactic lectures, clinical consultation, and the informal presence of PC clinicians, the team created a palliative care service in HM-BMT unit of the Western Pennsylvania Hospital in Pittsburgh. The following data were collected for each consult: referral reason, daily pain assessments, whether or not a “goals of care” conversation took place, and hospice enrollment. Lastly, satisfaction surveys were administered.
 

Results During the program, 392 PC consultations were provided to 256 unique patients. Of these 256 patients, the PC clinicians documented the first goals of care conversations in 67% of patients (n = 172). Of the 278 consults referred for pain, 70% (n = 194) involved reports of unacceptable or very unacceptable pain at baseline. Sixty-six percent (n = 129) of these 194 consults involved reports of pain that was acceptable or very acceptable within 48 hours of consultation. In addition, the hospice referral rate grew from a pre-implementation rate of 5% to 41% (n = 67) of 165 patients who died during the period of program implementation. Lastly, hematological oncologists reported high levels of satisfaction with the program.
 

Limitations The main limitation of this project is that it was a single institution study.
 

Conclusion The successful integration of a PC team into a hematological malignancy unit suggests great potential for positive interdisciplinary collaboration between these two fields.
 

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

Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of “transfusion culture” in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades.

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

Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of “transfusion culture” in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades.

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

Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of “transfusion culture” in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades.

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