Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Ever since the 2001 attack on the World Trade Center, I have associated a bright, sunny day with disaster. I vividly remember what a beautiful morning that was -- a crystal blue cloudless sky, low humidity, and a cool, comfortable temperature. Who could be unhappy on such a marvelous day?

On the other hand, my experience living in a northern climate taught me that winter was another story. Getting up in the dark to go to school or work was a miserable experience, followed by coming home in the dark and endless hours of biting cold and bitter nights. I was not surprised to learn later in my residency training about seasonal affective disorder and about the effects of light on mood. With this background, I felt primed to write a column about a new study, "Direct Effect of Sunshine on Suicide" (JAMA Psychiatry 2014 Sept. 10 [doi:10.1001/jamapsychiatry.2014.1198]).

In this study, investigators looked at public records of confirmed suicides in Austria between January 1970 and May 2010.They gathered 40 years of daily sunlight data from 86 meteorological stations. The amount of sunlight was defined as the duration of time that light intensity was higher than 120 watts per square meter, which apparently is the amount of light typically seen just after sunrise or just before sunset. Using this information, they compared daily suicide rates with the average daily duration of sunshine. Since sunlight varies in both duration and intensity over the seasons, the researchers used statistical methods to compensate for this, which distinguished this work from previous similar suicide studies. The authors then compared suicide rates by gender and method.

There were 69,462 suicide deaths, the majority through violent means such as hanging, drowning, shooting, or jumping. Only a quarter of the deaths were through nonviolent means such as poisoning. A significant correlation was found between the daily suicide rate and the daily duration of sunshine, but the surprising result was that sunshine appeared to have both a provocative and a palliative effect. Suicide rates climbed with increasing sunshine during the 10 days leading up to a suicide for suicides as a whole, for suicide through violent means, and for women. Sunlight had no effect on suicides for nonviolent deaths.

As a group, there was a negative correlation with deaths for the 14-60 days prior to a given suicide. Violent suicides were less likely during this time. The effects of sunshine also were specific to gender. There was a negative correlation, or apparently a protective effect, for men but not for women in the preceding 14-60 days.

Many physiologic reasons explain why light can affect mood, such as disruption of circadian rhythms and altered melatonin levels, or disturbances in serotonin or monoamine systems. There have also been social explanations for why suicides show seasonal variation. The "winter blues" have been explained by the stress of holiday preparation and its associated high expectations, family conflict, and increased alcohol use around this time. The authors concluded that one reason sunlight may increase suicide rates is that sunlight may improve motivation before lifting mood, giving a person the impetus to act on self-destructive impulses.

How this relates to the use of light boxes to treat seasonal affective disorder remains to be seen. Traditionally, this intervention is favored because of the relatively few associated hazards and side effects compared to pharmacotherapy. This risk-benefit ratio may need to be reassessed as more studies address the sunlight-suicide connection. Still, given that these devices are not Food and Drug Administration‑regulated or approved, I doubt we will be seeing the equivalent of a “black box” warning anytime in the near future.

Dr. Hanson is a forensic psychiatrist and coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work.” The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson's employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Plasmodium oocysts

(blue) in mosquito gut

Credit: Antoine Nicot

and Jacques Denoyelle

Experiments in canaries have shown that Plasmodium parasites react when non-infected mosquitoes bite their hosts, and the parasite responses increase transmission to the mosquito.

Like many other parasites, Plasmodium goes through a phase of chronic infection during which most of the parasites are in a dormant stage, and parasite numbers in the blood are very low.

Every now and then, however, the parasites “relapse,” and numbers increase, but the cause of this is not well understood.

So researchers set out to determine whether bites from non-infected mosquitoes can trigger relapses in Plasmodium during chronic infections, and whether relapses are associated with higher rates of transmission to the vector, ie, infection of the mosquitoes.

Sylvain Gandon, PhD, of the Université de Montpellier in France, and his colleagues described this research in PLOS Pathogens.

Specifically, the researchers studied the interaction between Plasmodium relictum, the parasite responsible for most cases of bird malaria in European songbirds, and its natural vector, a mosquito called Culex pipiens.

The team infected domestic canaries with P relictum and tested whether bites from uninfected Culex mosquitoes could trigger malaria relapses during chronic infection.

Indeed, parasite numbers in the blood routinely increased after the canaries were bitten. Moreover, the higher parasite loads following mosquito bites translated into higher infection rates in the mosquitoes.

The researchers therefore concluded that P relictum has the ability to boost its own transmission during the chronic phase of the vertebrate infection after being exposed to mosquito bites.

Although it is unclear if this also occurs in humans, the team suggested that better understanding of this phenomenon could eventually improve malaria control.

They also pointed out that many other pathogens alternate between acute and dormant phases. So better understanding of the ecological determinants and evolutionary forces governing parasite relapses could have wide-ranging applications.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Aspergillus fumigatus

WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.

Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).

The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.

Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).

Patient characteristics and safety outcomes

Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.

In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).

Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.

The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.

The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.

However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.

Response and mortality

All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.

All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.

For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.

In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.

“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.

ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.

The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD.

Skin biopsy showing GVHD

Credit: PLOS ONE

Results of a retrospective study have revealed factors that appear to increase the risk of vitiligo and alopecia areata (AA) in patients who develop chronic graft-vs-host disease (cGVHD) after a stem cell transplant.

Multivariable analysis suggested that a female donor to male recipient sex mismatch and positive test results for anticardiolipin immunoglobulin G (ACA-IgG) were both significantly associated with vitiligo and/or AA.

This research was published in JAMA Dermatology.

Edward W. Cowen, MD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues conducted the study in 282 adult and pediatric patients with cGVHD.

Fifteen of the patients (5.3%) had vitiligo and/or AA. One patient had only AA, 1 had vitiligo and AA, and the rest had vitiligo alone. The median age of these patients at enrollment was 38 years (range, 9-69 years), and most were male (n=10).

Most patients had received a transplant to treat chronic myelogenous leukemia (n=5) or acute leukemia/myelodysplastic syndrome (n=5). Most patients (n=13) had an HLA-identical donor and received a peripheral blood stem cell transplant (n=9).

Eleven patients had concomitant skin cGVHD at the time of evaluation, and it was most often sclerotic-type cGVHD (n=9).

For the 5 vitiligo patients in whom the onset of skin depigmentation was documented, pigment changes occurred at a median of 41 months (range, 24-84) after transplant.

Depigmentation was classic periorbital, perioral, acrofacial involvement in 6 patients, generalized in 6 patients, and torso-predominant in 2 patients. Trichrome vitiligo was present in 3 patients, and poliosis occurred in 5 patients. In both AA patients, hair loss was localized to the scalp.

The researchers evaluated demographic, clinical, and laboratory data from these patients, and used univariate and multivariable logistic regression analyses to identify risk factors for vitiligo and AA.

Univariate analysis suggested the following factors were significantly associated with vitiligo and/or AA: female donor to male recipient sex mismatch (P=0.003), positive test results for ACA-IgG (P=0.03) or antiparietal antibody (P=0.049), elevated CD19 (P=0.045), and normal or elevated IgG (P=0.02).

However, only positive ACA-IgG results and female donor to male recipient mismatch retained significance in multivariable analysis (P=0.01 and P=0.003, respectively).

The researchers said additional studies are needed to clarify whether these risk factors can lead to a better understanding of the pathomechanisms of cGVHD.

Between the ongoing shortage of child psychiatrists, ever-evolving changes in health care policy and medical insurance, and documented increases in the rates of many psychiatric disorders, it can be difficult for pediatricians to define their role in delivering quality mental health care. To get some perspective on these issues, I talked with Dr. Joseph F. Hagan Jr., a pediatrician from Burlington, Vt. Dr. Hagan has been involved in shaping pediatric mental health care policy for years as the former chair of the American Academy of Pediatrics’ (AAP) Committee on the Psychosocial Aspects of Child & Family Health and current member of the Bright Futures Steering Committee. He is also running this year to be the president-elect of the national AAP.

Q: What do you see as some of the key issues affecting child mental health care?

A: One of the things I haven’t heard a lot about is that there are not enough therapists to see children. The system has traditionally been based upon procedures and not on time, and that’s a problem. Therapists get paid less than the shop rate of your local auto mechanic, and of course, anyone who sees children has to talk with schools and parents outside of the session. That’s nonbillable, and we wonder why nobody will see children. Mental health is part of health, and the earlier we invest, the bigger the return. Because our practice was certified as a Family Centered Medical Home and now has access to a Community Health Team, my life has changed because we now have services that we didn’t have before. The problem with screening in the past has been "What if you find something?" Now we have so much more to offer.

Q: How much should a pediatrician really be expected to know and do when it comes to child behavioral problems? Is there a floor of knowledge and skills when it comes to mental health that all pediatricians should attain?

A: I think there definitely is. I would say that this could happen in steps. The AAP’s Taskforce for Mental Health really helped lay this out, but we already knew this. Behavioral and mental health problems can be managed in our offices, and everyone ought to be able to manage the majority of children with attention-deficit/hyperactivity disorder (ADHD), but also those with oppositional defiant disorder, anxiety, and depression. There are certain mental health problems that are part of pediatrics. To refer a standard ADHD child is absurd, because it really is a day-to-day problem that needs to be managed in your primary care medical home. Everybody needs to know how to do that and do it well. It is a chronic illness, and you need to hang in there with these children. That’s the basic floor. I think the floor is extended in being able to identify postpartum depression because we know that’s crucial and to be able to identify families who are really struggling with social determinants of health. This is going to be a big push in the forthcoming edition of Bright Futures. I think you also need to be able to identify anxiety and depression and be able to take the first steps in that. And maybe you should know how to treat them with selective serotonin reuptake inhibitors (SSRIs) if that should become important. I think you also should be able to talk about preventive things and ought to know that there is this thing called CBT (cognitive-behavioral therapy), and which therapists are in town who do CBT. You’ve got to know your community nonmedication options and access them before you decide upon meds.

Q: Psychiatric medications certainly have become even more controversial lately. What advice do you have for pediatricians when they prescribe them?

A: Tell families the expected effects and potential side effects. If you don’t, Dr. Google will. Start low and go slow, but titrate until desired effect of recovery. Remember if you are 100% anxious and miserable, you’ll look and feel great when you’re only 50% anxious, but you’re still only halfway better! It’s also important to discuss with your patient when you start meds, how long you are going to continue them, lest they feel good and stop prematurely.

Q: There are a lot of efforts these days to extend the education of pediatricians and provide consulting back up while the patient remains directly in the care of pediatrician. Do you think those efforts are enough or should we be more focused on providing more psychiatrists and other mental health clinicians that pediatricians can refer to?

A: We need to be able to do this (mental health) work, but part of being successful is having someone to consult with and someone to refer to. Just like with cardiac or GI problems, there are cases we can take care of all by ourselves, cases in which we will need to reach out to a consultant for help, and cases that need referral. Yes, we need more child psychiatrists. Co-located and collaborative care are the best-case scenarios.

More information about mental health care from the American Academy of Pediatrics can be found if you click here.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

Between the ongoing shortage of child psychiatrists, ever-evolving changes in health care policy and medical insurance, and documented increases in the rates of many psychiatric disorders, it can be difficult for pediatricians to define their role in delivering quality mental health care. To get some perspective on these issues, I talked with Dr. Joseph F. Hagan Jr., a pediatrician from Burlington, Vt. Dr. Hagan has been involved in shaping pediatric mental health care policy for years as the former chair of the American Academy of Pediatrics’ (AAP) Committee on the Psychosocial Aspects of Child & Family Health and current member of the Bright Futures Steering Committee. He is also running this year to be the president-elect of the national AAP.

Q: What do you see as some of the key issues affecting child mental health care?

A: One of the things I haven’t heard a lot about is that there are not enough therapists to see children. The system has traditionally been based upon procedures and not on time, and that’s a problem. Therapists get paid less than the shop rate of your local auto mechanic, and of course, anyone who sees children has to talk with schools and parents outside of the session. That’s nonbillable, and we wonder why nobody will see children. Mental health is part of health, and the earlier we invest, the bigger the return. Because our practice was certified as a Family Centered Medical Home and now has access to a Community Health Team, my life has changed because we now have services that we didn’t have before. The problem with screening in the past has been "What if you find something?" Now we have so much more to offer.

Q: How much should a pediatrician really be expected to know and do when it comes to child behavioral problems? Is there a floor of knowledge and skills when it comes to mental health that all pediatricians should attain?

A: I think there definitely is. I would say that this could happen in steps. The AAP’s Taskforce for Mental Health really helped lay this out, but we already knew this. Behavioral and mental health problems can be managed in our offices, and everyone ought to be able to manage the majority of children with attention-deficit/hyperactivity disorder (ADHD), but also those with oppositional defiant disorder, anxiety, and depression. There are certain mental health problems that are part of pediatrics. To refer a standard ADHD child is absurd, because it really is a day-to-day problem that needs to be managed in your primary care medical home. Everybody needs to know how to do that and do it well. It is a chronic illness, and you need to hang in there with these children. That’s the basic floor. I think the floor is extended in being able to identify postpartum depression because we know that’s crucial and to be able to identify families who are really struggling with social determinants of health. This is going to be a big push in the forthcoming edition of Bright Futures. I think you also need to be able to identify anxiety and depression and be able to take the first steps in that. And maybe you should know how to treat them with selective serotonin reuptake inhibitors (SSRIs) if that should become important. I think you also should be able to talk about preventive things and ought to know that there is this thing called CBT (cognitive-behavioral therapy), and which therapists are in town who do CBT. You’ve got to know your community nonmedication options and access them before you decide upon meds.

Q: Psychiatric medications certainly have become even more controversial lately. What advice do you have for pediatricians when they prescribe them?

A: Tell families the expected effects and potential side effects. If you don’t, Dr. Google will. Start low and go slow, but titrate until desired effect of recovery. Remember if you are 100% anxious and miserable, you’ll look and feel great when you’re only 50% anxious, but you’re still only halfway better! It’s also important to discuss with your patient when you start meds, how long you are going to continue them, lest they feel good and stop prematurely.

Q: There are a lot of efforts these days to extend the education of pediatricians and provide consulting back up while the patient remains directly in the care of pediatrician. Do you think those efforts are enough or should we be more focused on providing more psychiatrists and other mental health clinicians that pediatricians can refer to?

A: We need to be able to do this (mental health) work, but part of being successful is having someone to consult with and someone to refer to. Just like with cardiac or GI problems, there are cases we can take care of all by ourselves, cases in which we will need to reach out to a consultant for help, and cases that need referral. Yes, we need more child psychiatrists. Co-located and collaborative care are the best-case scenarios.

More information about mental health care from the American Academy of Pediatrics can be found if you click here.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

Between the ongoing shortage of child psychiatrists, ever-evolving changes in health care policy and medical insurance, and documented increases in the rates of many psychiatric disorders, it can be difficult for pediatricians to define their role in delivering quality mental health care. To get some perspective on these issues, I talked with Dr. Joseph F. Hagan Jr., a pediatrician from Burlington, Vt. Dr. Hagan has been involved in shaping pediatric mental health care policy for years as the former chair of the American Academy of Pediatrics’ (AAP) Committee on the Psychosocial Aspects of Child & Family Health and current member of the Bright Futures Steering Committee. He is also running this year to be the president-elect of the national AAP.

Q: What do you see as some of the key issues affecting child mental health care?

A: One of the things I haven’t heard a lot about is that there are not enough therapists to see children. The system has traditionally been based upon procedures and not on time, and that’s a problem. Therapists get paid less than the shop rate of your local auto mechanic, and of course, anyone who sees children has to talk with schools and parents outside of the session. That’s nonbillable, and we wonder why nobody will see children. Mental health is part of health, and the earlier we invest, the bigger the return. Because our practice was certified as a Family Centered Medical Home and now has access to a Community Health Team, my life has changed because we now have services that we didn’t have before. The problem with screening in the past has been "What if you find something?" Now we have so much more to offer.

Q: How much should a pediatrician really be expected to know and do when it comes to child behavioral problems? Is there a floor of knowledge and skills when it comes to mental health that all pediatricians should attain?

A: I think there definitely is. I would say that this could happen in steps. The AAP’s Taskforce for Mental Health really helped lay this out, but we already knew this. Behavioral and mental health problems can be managed in our offices, and everyone ought to be able to manage the majority of children with attention-deficit/hyperactivity disorder (ADHD), but also those with oppositional defiant disorder, anxiety, and depression. There are certain mental health problems that are part of pediatrics. To refer a standard ADHD child is absurd, because it really is a day-to-day problem that needs to be managed in your primary care medical home. Everybody needs to know how to do that and do it well. It is a chronic illness, and you need to hang in there with these children. That’s the basic floor. I think the floor is extended in being able to identify postpartum depression because we know that’s crucial and to be able to identify families who are really struggling with social determinants of health. This is going to be a big push in the forthcoming edition of Bright Futures. I think you also need to be able to identify anxiety and depression and be able to take the first steps in that. And maybe you should know how to treat them with selective serotonin reuptake inhibitors (SSRIs) if that should become important. I think you also should be able to talk about preventive things and ought to know that there is this thing called CBT (cognitive-behavioral therapy), and which therapists are in town who do CBT. You’ve got to know your community nonmedication options and access them before you decide upon meds.

Q: Psychiatric medications certainly have become even more controversial lately. What advice do you have for pediatricians when they prescribe them?

A: Tell families the expected effects and potential side effects. If you don’t, Dr. Google will. Start low and go slow, but titrate until desired effect of recovery. Remember if you are 100% anxious and miserable, you’ll look and feel great when you’re only 50% anxious, but you’re still only halfway better! It’s also important to discuss with your patient when you start meds, how long you are going to continue them, lest they feel good and stop prematurely.

Q: There are a lot of efforts these days to extend the education of pediatricians and provide consulting back up while the patient remains directly in the care of pediatrician. Do you think those efforts are enough or should we be more focused on providing more psychiatrists and other mental health clinicians that pediatricians can refer to?

A: We need to be able to do this (mental health) work, but part of being successful is having someone to consult with and someone to refer to. Just like with cardiac or GI problems, there are cases we can take care of all by ourselves, cases in which we will need to reach out to a consultant for help, and cases that need referral. Yes, we need more child psychiatrists. Co-located and collaborative care are the best-case scenarios.

More information about mental health care from the American Academy of Pediatrics can be found if you click here.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

SAN FRANCISCO – Dr. Eleftherios (Terry) Mamounas reviews the first day of the annual breast cancer symposium sponsored by the American Society of Clinical Oncology.

Key sessions covered the increasingly complex topic of genetic risk assessment and stirred up the debate about management of ductal carcinoma in situ (DCIS). Dr. Mamounas, professor of surgery at the University of Central Florida and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando, discusses the significance of atypical hyperplasia, including new data suggesting that the fourfold increased risk of developing breast cancer in women with ductal carcinoma in situ (DCIS) is not further worsened by having a family history of DCIS.

Among the top oral presentations, one study suggested that a nomogram helped predict the risk of locoregional recurrence in patients treated for breast cancer using accelerated partial-breast irradiation. Another study examined the effect of hormone receptor status and local treatment on overall survival for patients with early-stage breast cancer.

Dr. Mamounas also discusses his own study, which he presented at the meeting, showing lower rates of locoregional recurrence in patients who have a pathologic complete response to neoadjuvant therapy. He puts the findings in context with tips on how to incorporate pathologic complete response data into clinical practice.

A separate study reported some of the first data on complication rates after unilateral or bilateral mastectomy and reconstruction. Dr. Mamounas wraps up the day’s review by discussing sessions on the effect of luteinizing hormone-releasing hormone agonists during chemotherapy in preserving ovarian function, and on breast cancer prevention, including the use of aromatase inhibitors.

For more of the meeting’s highlights, see our video interviews with Dr. Hope S. Rugo discussing the events of the second and third days of the Breast Cancer Symposium. Dr. Rugo is director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Mamounas reported financial associations with Genomic Health, Genentech/Roche, Pfizer, GlaxoSmithKline, Eisai, Celgene, and GE Healthcare.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Dr. Eleftherios (Terry) Mamounas reviews the first day of the annual breast cancer symposium sponsored by the American Society of Clinical Oncology.

Key sessions covered the increasingly complex topic of genetic risk assessment and stirred up the debate about management of ductal carcinoma in situ (DCIS). Dr. Mamounas, professor of surgery at the University of Central Florida and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando, discusses the significance of atypical hyperplasia, including new data suggesting that the fourfold increased risk of developing breast cancer in women with ductal carcinoma in situ (DCIS) is not further worsened by having a family history of DCIS.

Among the top oral presentations, one study suggested that a nomogram helped predict the risk of locoregional recurrence in patients treated for breast cancer using accelerated partial-breast irradiation. Another study examined the effect of hormone receptor status and local treatment on overall survival for patients with early-stage breast cancer.

Dr. Mamounas also discusses his own study, which he presented at the meeting, showing lower rates of locoregional recurrence in patients who have a pathologic complete response to neoadjuvant therapy. He puts the findings in context with tips on how to incorporate pathologic complete response data into clinical practice.

A separate study reported some of the first data on complication rates after unilateral or bilateral mastectomy and reconstruction. Dr. Mamounas wraps up the day’s review by discussing sessions on the effect of luteinizing hormone-releasing hormone agonists during chemotherapy in preserving ovarian function, and on breast cancer prevention, including the use of aromatase inhibitors.

For more of the meeting’s highlights, see our video interviews with Dr. Hope S. Rugo discussing the events of the second and third days of the Breast Cancer Symposium. Dr. Rugo is director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Mamounas reported financial associations with Genomic Health, Genentech/Roche, Pfizer, GlaxoSmithKline, Eisai, Celgene, and GE Healthcare.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Dr. Eleftherios (Terry) Mamounas reviews the first day of the annual breast cancer symposium sponsored by the American Society of Clinical Oncology.

Key sessions covered the increasingly complex topic of genetic risk assessment and stirred up the debate about management of ductal carcinoma in situ (DCIS). Dr. Mamounas, professor of surgery at the University of Central Florida and medical director of the comprehensive breast program at the University of Florida Health Cancer Center, both in Orlando, discusses the significance of atypical hyperplasia, including new data suggesting that the fourfold increased risk of developing breast cancer in women with ductal carcinoma in situ (DCIS) is not further worsened by having a family history of DCIS.

Among the top oral presentations, one study suggested that a nomogram helped predict the risk of locoregional recurrence in patients treated for breast cancer using accelerated partial-breast irradiation. Another study examined the effect of hormone receptor status and local treatment on overall survival for patients with early-stage breast cancer.

Dr. Mamounas also discusses his own study, which he presented at the meeting, showing lower rates of locoregional recurrence in patients who have a pathologic complete response to neoadjuvant therapy. He puts the findings in context with tips on how to incorporate pathologic complete response data into clinical practice.

A separate study reported some of the first data on complication rates after unilateral or bilateral mastectomy and reconstruction. Dr. Mamounas wraps up the day’s review by discussing sessions on the effect of luteinizing hormone-releasing hormone agonists during chemotherapy in preserving ovarian function, and on breast cancer prevention, including the use of aromatase inhibitors.

For more of the meeting’s highlights, see our video interviews with Dr. Hope S. Rugo discussing the events of the second and third days of the Breast Cancer Symposium. Dr. Rugo is director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Mamounas reported financial associations with Genomic Health, Genentech/Roche, Pfizer, GlaxoSmithKline, Eisai, Celgene, and GE Healthcare.

[email protected]

On Twitter @sherryboschert

Active-duty military personnel, members of the National Guard and reserve, veterans, military families, and health professionals all are provided unique resources for ongoing support when they visit the Real Warriors Campaign at http://www.realwarriors.net, launched by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. The public awareness campaign is intended “to promote the processes of building resilience, facilitating recovery, and supporting reintegration of returning service members, veterans, and their families.”

The Active Duty menu addresses broad topics, such as Signs and Symptoms of Combat Stress, Building Resilience, and After Deployment. Additional topics are drilled down for active-duty members of the Army, Navy, Marine Corps, and Air Force.

National Guard and reserve members are provided advice to assist in preparation for deployment, a reintegration guide for communicating with employers and family members, and coping and support.

The Veterans page directs users to resources provided through the VA; meanwhile, health care professionals are directed to TRICARE information, evidence-based treatment guidelines for PTSD and TBI, and original presentations of tools and tips, many of which can be ordered online at no cost.

Active-duty military personnel, members of the National Guard and reserve, veterans, military families, and health professionals all are provided unique resources for ongoing support when they visit the Real Warriors Campaign at http://www.realwarriors.net, launched by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. The public awareness campaign is intended “to promote the processes of building resilience, facilitating recovery, and supporting reintegration of returning service members, veterans, and their families.”

The Active Duty menu addresses broad topics, such as Signs and Symptoms of Combat Stress, Building Resilience, and After Deployment. Additional topics are drilled down for active-duty members of the Army, Navy, Marine Corps, and Air Force.

National Guard and reserve members are provided advice to assist in preparation for deployment, a reintegration guide for communicating with employers and family members, and coping and support.

The Veterans page directs users to resources provided through the VA; meanwhile, health care professionals are directed to TRICARE information, evidence-based treatment guidelines for PTSD and TBI, and original presentations of tools and tips, many of which can be ordered online at no cost.

Active-duty military personnel, members of the National Guard and reserve, veterans, military families, and health professionals all are provided unique resources for ongoing support when they visit the Real Warriors Campaign at http://www.realwarriors.net, launched by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. The public awareness campaign is intended “to promote the processes of building resilience, facilitating recovery, and supporting reintegration of returning service members, veterans, and their families.”

The Active Duty menu addresses broad topics, such as Signs and Symptoms of Combat Stress, Building Resilience, and After Deployment. Additional topics are drilled down for active-duty members of the Army, Navy, Marine Corps, and Air Force.

National Guard and reserve members are provided advice to assist in preparation for deployment, a reintegration guide for communicating with employers and family members, and coping and support.

The Veterans page directs users to resources provided through the VA; meanwhile, health care professionals are directed to TRICARE information, evidence-based treatment guidelines for PTSD and TBI, and original presentations of tools and tips, many of which can be ordered online at no cost.

Genome testing

Credit: NIGMS

Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.

The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.

Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.

And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).

These findings appear in BMC Medical Genomics.

To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.

“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.

The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.

Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.

Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.

Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.

On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).

Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.

“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”

Genome testing

Credit: NIGMS

Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.

The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.

Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.

And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).

These findings appear in BMC Medical Genomics.

To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.

“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.

The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.

Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.

Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.

Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.

On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).

Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.

“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”

Genome testing

Credit: NIGMS

Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.

The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.

Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.

And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).

These findings appear in BMC Medical Genomics.

To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.

“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.

The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.

Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.

Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.

Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.

On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).

Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.

“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”

The National Institutes of Health has launched an online public database called ClinRegs, which includes country-specific information on

clinical research regulations.

ClinRegs currently provides information for 12 countries, but additional countries will likely be added in the future.

The goal of ClinRegs is to make it easier for investigators to find and understand country-specific requirements on topics such as clinical trial application submission and ethics committee approvals.

The database allows users to review regulatory requirements in 7 topic areas, including informed consent practices and trial sponsorship.

The site was created—and will be updated—by the National Institute of Allergy and Infectious Diseases.

The National Institutes of Health has launched an online public database called ClinRegs, which includes country-specific information on

clinical research regulations.

ClinRegs currently provides information for 12 countries, but additional countries will likely be added in the future.

The goal of ClinRegs is to make it easier for investigators to find and understand country-specific requirements on topics such as clinical trial application submission and ethics committee approvals.

The database allows users to review regulatory requirements in 7 topic areas, including informed consent practices and trial sponsorship.

The site was created—and will be updated—by the National Institute of Allergy and Infectious Diseases.

The National Institutes of Health has launched an online public database called ClinRegs, which includes country-specific information on

clinical research regulations.

ClinRegs currently provides information for 12 countries, but additional countries will likely be added in the future.

The goal of ClinRegs is to make it easier for investigators to find and understand country-specific requirements on topics such as clinical trial application submission and ethics committee approvals.

The database allows users to review regulatory requirements in 7 topic areas, including informed consent practices and trial sponsorship.

The site was created—and will be updated—by the National Institute of Allergy and Infectious Diseases.