Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

 

 

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

 

 

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The development of infections from mycobacteria and fungi endemic to U.S. regions in patients taking tumor necrosis factor–alpha inhibitors (TNFIs) is rare and is not influenced by prescreening of targeted infections, research suggests.

A case-control study of 30,772 patients taking TNFIs showed that only 158 (0.51%) patients developed the fungal and/or mycobacterial infections targeted in this study, with tuberculosis and histoplasmosis being the most common infections.

Targeted infections were nontuberculous mycobacterial infection, blastomycosis, coccidioidomyocosis, cryptococcal infection, histoplasmosis, pneumocystosis, tuberculosis disease, and unspecified fungal infection.

Prednisone was the only predictive factor for infection and was associated with a twofold increase in the likelihood of patients seeking medical attention for a fungal or mycobacterial infection, which the authors said was supported by previous research, according to a paper published online in Arthritis & Rheumatology.

“Thus, the question remains if the increased infection rates are related solely to the use of the glucocorticoids or the active disease for which the medication is being prescribed,” wrote Elizabeth Salt, Ph.D., of the University of Kentucky, Lexington, and coauthors (Arthritis Rheumatol. 2015 Oct 16 doi: 10.1002/art.39462).

Researchers also noted that sulfamethoxazole-trimethoprim was associated with a nonsignificant 45% increase in the likelihood of requiring medical care, compared with controls.

“It is possible that providers recognized the infectious risk of this population and made attempts at controlling infectious processes among those most vulnerable.”

The study was supported by the National Institutes of Health. There were no conflicts of interest declared.

The development of infections from mycobacteria and fungi endemic to U.S. regions in patients taking tumor necrosis factor–alpha inhibitors (TNFIs) is rare and is not influenced by prescreening of targeted infections, research suggests.

A case-control study of 30,772 patients taking TNFIs showed that only 158 (0.51%) patients developed the fungal and/or mycobacterial infections targeted in this study, with tuberculosis and histoplasmosis being the most common infections.

Targeted infections were nontuberculous mycobacterial infection, blastomycosis, coccidioidomyocosis, cryptococcal infection, histoplasmosis, pneumocystosis, tuberculosis disease, and unspecified fungal infection.

Prednisone was the only predictive factor for infection and was associated with a twofold increase in the likelihood of patients seeking medical attention for a fungal or mycobacterial infection, which the authors said was supported by previous research, according to a paper published online in Arthritis & Rheumatology.

“Thus, the question remains if the increased infection rates are related solely to the use of the glucocorticoids or the active disease for which the medication is being prescribed,” wrote Elizabeth Salt, Ph.D., of the University of Kentucky, Lexington, and coauthors (Arthritis Rheumatol. 2015 Oct 16 doi: 10.1002/art.39462).

Researchers also noted that sulfamethoxazole-trimethoprim was associated with a nonsignificant 45% increase in the likelihood of requiring medical care, compared with controls.

“It is possible that providers recognized the infectious risk of this population and made attempts at controlling infectious processes among those most vulnerable.”

The study was supported by the National Institutes of Health. There were no conflicts of interest declared.

The development of infections from mycobacteria and fungi endemic to U.S. regions in patients taking tumor necrosis factor–alpha inhibitors (TNFIs) is rare and is not influenced by prescreening of targeted infections, research suggests.

A case-control study of 30,772 patients taking TNFIs showed that only 158 (0.51%) patients developed the fungal and/or mycobacterial infections targeted in this study, with tuberculosis and histoplasmosis being the most common infections.

Targeted infections were nontuberculous mycobacterial infection, blastomycosis, coccidioidomyocosis, cryptococcal infection, histoplasmosis, pneumocystosis, tuberculosis disease, and unspecified fungal infection.

Prednisone was the only predictive factor for infection and was associated with a twofold increase in the likelihood of patients seeking medical attention for a fungal or mycobacterial infection, which the authors said was supported by previous research, according to a paper published online in Arthritis & Rheumatology.

“Thus, the question remains if the increased infection rates are related solely to the use of the glucocorticoids or the active disease for which the medication is being prescribed,” wrote Elizabeth Salt, Ph.D., of the University of Kentucky, Lexington, and coauthors (Arthritis Rheumatol. 2015 Oct 16 doi: 10.1002/art.39462).

Researchers also noted that sulfamethoxazole-trimethoprim was associated with a nonsignificant 45% increase in the likelihood of requiring medical care, compared with controls.

“It is possible that providers recognized the infectious risk of this population and made attempts at controlling infectious processes among those most vulnerable.”

The study was supported by the National Institutes of Health. There were no conflicts of interest declared.

The delicate balance involved in providing hospitalized patients with needed anticoagulant, anti-platelet, and thrombolytic therapies for stroke and possible cardiac complications while minimizing bleed risks was explored by several speakers at the University of California San Francisco’s annual Management of the Hospitalized Patient Conference.

“These are dynamic issues and they’re moving all the time,” said Tracy Minichiello, MD, a former hospitalist who now runs the Anticoagulation and Thrombosis Service at the San Francisco VA Medical Center. Dosing and monitoring choices for physicians have grown more complicated with the new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), and she said another balancing act is emerging in hospitals trying to avoid unnecessary and wasteful treatments.

“There is interest on both sides of that question,” Dr. Minichiello said, adding the stakes are high. “We don’t want to miss the diagnosis of pulmonary embolisms, which can be difficult to catch. But now there’s more discussion of the other side of the issue—over-diagnosis and over-treatment—where we’re also trying to avoid, for example, overuse of CT scans.”

Another major thrust of Dr. Minichiello’s presentations involved bridging therapies, the application of a parenteral, short-acting anticoagulant therapy during the temporary interruption of warfarin anticoagulation for an invasive procedure. Bridging decreases stroke and embolism risk, but with an increased risk for bleeding.

“Full intensity bridging therapy for anticoagulation potentially can do more harm than good,” she said, noting a dearth of data to support mortality benefits of bridging therapy.

Literature increasingly recommends hospitalists be more selective about the use of bridging therapies that might have been employed reflexively in the past, she noted.

“[Hospitalists] must be mindful of the risks and benefits,” she said.

Physicians should also think twice about concomitant antiplatelet therapy like aspirin with anticoagulants. “We need to work collaboratively with our cardiology colleagues when a patient is on two or three of these therapies,” she said. “Recommendations in this area are in evolution.”

Elise Bouchard, MD, an internist at Centre Maria-Chapdelaine in Dolbeau-Mistassini, Quebec, attended Dr. Minichiello’s breakout session on challenging cases.

“I learned that we shouldn’t use aspirin with Coumadin or other anticoagulants, except for cases like acute coronary syndrome,” Dr. Bouchard said. She also explained a number of her patients with cancer, for example, need anticoagulation treatment and hate getting another injection, so she tries when possible to offer the oral anticoagulants.

Dr. Minichiello works with hospitalists at the San Francisco VA who seek consults around procedures, anticoagulant choices, and when to restart treatments.

“Most hospitalists don’t have access to a service like ours, although they might be able to call on a hematology consult service [or pharmacist],” she said. She suggested hospitalists trying to develop their own evidenced-based protocols use websites like the University of Washington’s anticoagulation service website, or the American Society of Health System Pharmacists’ anticoagulation resource center. TH

The delicate balance involved in providing hospitalized patients with needed anticoagulant, anti-platelet, and thrombolytic therapies for stroke and possible cardiac complications while minimizing bleed risks was explored by several speakers at the University of California San Francisco’s annual Management of the Hospitalized Patient Conference.

“These are dynamic issues and they’re moving all the time,” said Tracy Minichiello, MD, a former hospitalist who now runs the Anticoagulation and Thrombosis Service at the San Francisco VA Medical Center. Dosing and monitoring choices for physicians have grown more complicated with the new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), and she said another balancing act is emerging in hospitals trying to avoid unnecessary and wasteful treatments.

“There is interest on both sides of that question,” Dr. Minichiello said, adding the stakes are high. “We don’t want to miss the diagnosis of pulmonary embolisms, which can be difficult to catch. But now there’s more discussion of the other side of the issue—over-diagnosis and over-treatment—where we’re also trying to avoid, for example, overuse of CT scans.”

Another major thrust of Dr. Minichiello’s presentations involved bridging therapies, the application of a parenteral, short-acting anticoagulant therapy during the temporary interruption of warfarin anticoagulation for an invasive procedure. Bridging decreases stroke and embolism risk, but with an increased risk for bleeding.

“Full intensity bridging therapy for anticoagulation potentially can do more harm than good,” she said, noting a dearth of data to support mortality benefits of bridging therapy.

Literature increasingly recommends hospitalists be more selective about the use of bridging therapies that might have been employed reflexively in the past, she noted.

“[Hospitalists] must be mindful of the risks and benefits,” she said.

Physicians should also think twice about concomitant antiplatelet therapy like aspirin with anticoagulants. “We need to work collaboratively with our cardiology colleagues when a patient is on two or three of these therapies,” she said. “Recommendations in this area are in evolution.”

Elise Bouchard, MD, an internist at Centre Maria-Chapdelaine in Dolbeau-Mistassini, Quebec, attended Dr. Minichiello’s breakout session on challenging cases.

“I learned that we shouldn’t use aspirin with Coumadin or other anticoagulants, except for cases like acute coronary syndrome,” Dr. Bouchard said. She also explained a number of her patients with cancer, for example, need anticoagulation treatment and hate getting another injection, so she tries when possible to offer the oral anticoagulants.

Dr. Minichiello works with hospitalists at the San Francisco VA who seek consults around procedures, anticoagulant choices, and when to restart treatments.

“Most hospitalists don’t have access to a service like ours, although they might be able to call on a hematology consult service [or pharmacist],” she said. She suggested hospitalists trying to develop their own evidenced-based protocols use websites like the University of Washington’s anticoagulation service website, or the American Society of Health System Pharmacists’ anticoagulation resource center. TH

The delicate balance involved in providing hospitalized patients with needed anticoagulant, anti-platelet, and thrombolytic therapies for stroke and possible cardiac complications while minimizing bleed risks was explored by several speakers at the University of California San Francisco’s annual Management of the Hospitalized Patient Conference.

“These are dynamic issues and they’re moving all the time,” said Tracy Minichiello, MD, a former hospitalist who now runs the Anticoagulation and Thrombosis Service at the San Francisco VA Medical Center. Dosing and monitoring choices for physicians have grown more complicated with the new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), and she said another balancing act is emerging in hospitals trying to avoid unnecessary and wasteful treatments.

“There is interest on both sides of that question,” Dr. Minichiello said, adding the stakes are high. “We don’t want to miss the diagnosis of pulmonary embolisms, which can be difficult to catch. But now there’s more discussion of the other side of the issue—over-diagnosis and over-treatment—where we’re also trying to avoid, for example, overuse of CT scans.”

Another major thrust of Dr. Minichiello’s presentations involved bridging therapies, the application of a parenteral, short-acting anticoagulant therapy during the temporary interruption of warfarin anticoagulation for an invasive procedure. Bridging decreases stroke and embolism risk, but with an increased risk for bleeding.

“Full intensity bridging therapy for anticoagulation potentially can do more harm than good,” she said, noting a dearth of data to support mortality benefits of bridging therapy.

Literature increasingly recommends hospitalists be more selective about the use of bridging therapies that might have been employed reflexively in the past, she noted.

“[Hospitalists] must be mindful of the risks and benefits,” she said.

Physicians should also think twice about concomitant antiplatelet therapy like aspirin with anticoagulants. “We need to work collaboratively with our cardiology colleagues when a patient is on two or three of these therapies,” she said. “Recommendations in this area are in evolution.”

Elise Bouchard, MD, an internist at Centre Maria-Chapdelaine in Dolbeau-Mistassini, Quebec, attended Dr. Minichiello’s breakout session on challenging cases.

“I learned that we shouldn’t use aspirin with Coumadin or other anticoagulants, except for cases like acute coronary syndrome,” Dr. Bouchard said. She also explained a number of her patients with cancer, for example, need anticoagulation treatment and hate getting another injection, so she tries when possible to offer the oral anticoagulants.

Dr. Minichiello works with hospitalists at the San Francisco VA who seek consults around procedures, anticoagulant choices, and when to restart treatments.

“Most hospitalists don’t have access to a service like ours, although they might be able to call on a hematology consult service [or pharmacist],” she said. She suggested hospitalists trying to develop their own evidenced-based protocols use websites like the University of Washington’s anticoagulation service website, or the American Society of Health System Pharmacists’ anticoagulation resource center. TH

The biological transition to puberty has always marked a critical point in a primary care pediatrician’s relationship to a patient. Adolescents’ capacity for abstract reasoning, their movement to autonomy, their nuanced sense of identity, their need for privacy, and their emerging sexuality together give the pediatrician an opportunity and a responsibility to create a safe place to talk. Your office can be an oasis from parents, peers, and a society that seems saturated with sexuality. You can be trusted more than the Internet and offer discussions that are leavened by your long-standing relationship with the patient.

The growing public awareness, acceptance, and legal standing given to gay, lesbian, bisexual, and transgender individuals represents welcome societal progress, and we sense that amidst this richer public conversation, a growing number of children and adolescents are presenting with questions or worries about their own emerging sexual orientation or gender identity. We would like to start with our key takeaway: Discussions about sexual orientation and gender identity do not require that you give answers or predict the future. Focus instead on being a curious, compassionate, and nonjudgmental listener, and you will be effective at helping your patient to better manage new, uncertain, and possibly stressful feelings.

Our focus today is how to create a safe setting and specifically how to ask about and discuss sexual orientation. Most teenagers will wonder at some point about their orientation. Studies suggest that among adults, 5%-10% are attracted to the same sex and 3% describe themselves as gay or bisexual. Such surveys are very challenging, though, and in our experience, these percentages are higher. Sexual orientation is believed to exist on a continuum rather than in a simple binary state – some people identify as purely homosexual or heterosexual, and the rest exist somewhere in the middle. Sharing this fact alone can offer a very helpful perspective to young people who are feeling pressure to “figure out” if they are gay or straight.

While sexual orientation describes whom a person is attracted to, gender identity is a person’s internal sense of his or her own gender. It emerges in childhood and becomes more rich and nuanced in adolescence and adulthood, and, like sexual orientation, it is also believed to exist on a continuum rather than in a simple binary state. Less than 0.1% of youth will experience gender dysphoria, or the pressing feeling that their gender identity is not the same as their phenotypic sex. While questions about gender identity should be approached with the same curious, compassionate, and nonjudgmental style, we will not discuss the management of patients with gender dysphoria here. It is a very complex (and controversial) topic. And, as a practical matter, sexual orientation will likely be a more common issue with your patients, whereas questions about gender identity will come up much less frequently.

It is worth knowing that there is a range of mental health issues that are associated with the stress of feeling comfortable with one’s sexual identity. There is some evidence that young people who identify as gay or bisexual have elevated risk for mood disorders (depression), anxiety disorders, conduct disorder, and substance use disorders, but this finding has not been consistent (Am J Public Health. 2010:100[12]; 2426-32). However, there is unequivocal evidence that there is an elevated risk for suicide attempts in lesbian, gay, or bisexual (LGB) youth above their heterosexual peers. One survey found that 9th-12th grade students who identified as LGB were up to seven times as likely to have a suicide attempt as were their peers who identify as heterosexual. This risk is especially pronounced in male adolescents and continues into adulthood, when there is an elevated risk for suicide completion among adult males who identify as homosexual, although not in adult females (J Homosex. 2011 Jan;58[1]:10-51). Importantly, the risk for suicide attempt in LGB adolescents remains elevated even in those adolescents without any diagnosable mental illness, likely attributable to the stresses of isolation, family conflict, stigmatization, or bullying that LGB adolescents are likely to experience.

Asking your early-adolescent patients in a calm and comfortable manner about sexual feelings builds an environment in which thoughts, feelings, and questions about sex and sexuality are more easily shared. It is important to find language that feels like yours, which you can use with ease. Perhaps starting with, “At about your age, I ask every patient of mine whether they are beginning to have sexual feelings. This is when you really want to be around someone, in a way that’s more powerful and different from even your favorite friend. Some people call it getting butterflies in your stomach.” If your patient recognizes what you are talking about, you might continue, “Do you feel attracted to boys or girls or both? Do you have those feelings about kids in your class or people you know, like a teacher? Perhaps about a celebrity in a TV show or a band?” You should absolutely reassure them, “You don’t have to talk about anything you do not want to, but you should know that this is a normal part of becoming a teenager. I talk about this a lot with patients who are younger and older than you are. I keep what we talk about very private, and sometimes this is the only place a teenager feels safe to ask questions.” If you start this process early enough – by the start of middle school – the patient will probably be a bit embarrassed or giggle and not talk much. But, by the next annual physical or the one after that, the issue will be more familiar and less charged. A meaningful discussion may start.

With patients who do describe feeling attracted to people of the same sex, more specific questions may be appropriate. You should expect these feelings to exist on a continuum: You may encounter a school-age child with great clarity about exactly whom she is attracted to and what that means, or an older teenager who is far less certain, responding to a less intense interest or having been told by a peer that he is probably gay. It can be powerfully reassuring to remind your patient that adolescence is when we start to figure out to whom we are attracted. They don’t have to decide, but just be aware of these feelings as they emerge, essentially getting to know themselves without any feelings of urgency or pressure. You might ask, “Have you wondered if you were gay or bisexual? Have you spoken to any friends about your feelings or have you experimented with a boy or girl to try and figure this out?” It’s very helpful if you ask if they are worried or stressed by these feelings. Some young people will suffer from internalized homophobia, which may be helped by your accepting stance or may require a referral for more ongoing support. It can be valuable to find out if they are dating people of the same sex, or if their “relationships” have all been online. While this “virtual” dating may seem safer, it may not help them better understand themselves and may expose them to exploitation or predatory behavior. If your patient is sexually active, you should be comfortable talking with them about the risks of unprotected sex and same-sex safe-sex practices.

It is particularly important to ask your adolescent LGB patient about whom they have told, and what responses have they gotten. The presence of good friends and loving family members is critical to all adolescents’ emotional well-being. If they have talked about their sexual orientation with their peers, have their friends been supportive, or has it left them more isolated at school? You should find out if they have been teased or bullied, and ask specifically about online teasing or harassment. If they are being bullied, how have they handled that? Find out also if they feel free to ask or talk about this subject with their parents. If not, try to understand if they are simply embarrassed and unsure how to bring it up, or if there is a strong sense that they will be shamed or even rejected by their parents. If the parents are truly shaming or rejecting, it will be critical to consider what kind of support may be necessary. Teens who are facing isolation or bullying at school may benefit from resources such as a gay-straight student alliance or a community organization dedicated to issues facing LGB youth. For patients who are facing hostile or rejecting parents, it can be protective to connect them with a therapist as well, as you are mindful of their marked isolation and subsequently heightened risk for mood problems and even suicide attempts.

Along a similar vein, it is very important that you are aware of your own comfort level with these issues. While discussing sexual orientation may feel awkward if it is new for you, it is important to be realistic if you cannot be supportive of your patients who are gay. If for religious or other reasons you are not comfortable talking about sexual orientation in an accepting, nonjudgmental manner, you should seek guidance on how to thoughtfully care for your LGB patients or appropriately refer them to someone who can provide a more-supportive treatment setting.

When you create an office that makes sexuality a safe topic for discussion, you should expect that you will hear questions or concerns about which you yourself may not know the answers. Do not panic, just maintain your posture of being a curious, compassionate, and nonjudgmental listener, and then look for the answers. We are delighted this news organization has devoted a column to the optimal care of LGBT youth (LGBT Youth Consult) and encourage the primary care pediatrician to “never to worry alone,” and instead get some advice and expert teammates when dealing with these complex and important issues.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, in Newton, Mass. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.

The biological transition to puberty has always marked a critical point in a primary care pediatrician’s relationship to a patient. Adolescents’ capacity for abstract reasoning, their movement to autonomy, their nuanced sense of identity, their need for privacy, and their emerging sexuality together give the pediatrician an opportunity and a responsibility to create a safe place to talk. Your office can be an oasis from parents, peers, and a society that seems saturated with sexuality. You can be trusted more than the Internet and offer discussions that are leavened by your long-standing relationship with the patient.

The growing public awareness, acceptance, and legal standing given to gay, lesbian, bisexual, and transgender individuals represents welcome societal progress, and we sense that amidst this richer public conversation, a growing number of children and adolescents are presenting with questions or worries about their own emerging sexual orientation or gender identity. We would like to start with our key takeaway: Discussions about sexual orientation and gender identity do not require that you give answers or predict the future. Focus instead on being a curious, compassionate, and nonjudgmental listener, and you will be effective at helping your patient to better manage new, uncertain, and possibly stressful feelings.

Our focus today is how to create a safe setting and specifically how to ask about and discuss sexual orientation. Most teenagers will wonder at some point about their orientation. Studies suggest that among adults, 5%-10% are attracted to the same sex and 3% describe themselves as gay or bisexual. Such surveys are very challenging, though, and in our experience, these percentages are higher. Sexual orientation is believed to exist on a continuum rather than in a simple binary state – some people identify as purely homosexual or heterosexual, and the rest exist somewhere in the middle. Sharing this fact alone can offer a very helpful perspective to young people who are feeling pressure to “figure out” if they are gay or straight.

While sexual orientation describes whom a person is attracted to, gender identity is a person’s internal sense of his or her own gender. It emerges in childhood and becomes more rich and nuanced in adolescence and adulthood, and, like sexual orientation, it is also believed to exist on a continuum rather than in a simple binary state. Less than 0.1% of youth will experience gender dysphoria, or the pressing feeling that their gender identity is not the same as their phenotypic sex. While questions about gender identity should be approached with the same curious, compassionate, and nonjudgmental style, we will not discuss the management of patients with gender dysphoria here. It is a very complex (and controversial) topic. And, as a practical matter, sexual orientation will likely be a more common issue with your patients, whereas questions about gender identity will come up much less frequently.

It is worth knowing that there is a range of mental health issues that are associated with the stress of feeling comfortable with one’s sexual identity. There is some evidence that young people who identify as gay or bisexual have elevated risk for mood disorders (depression), anxiety disorders, conduct disorder, and substance use disorders, but this finding has not been consistent (Am J Public Health. 2010:100[12]; 2426-32). However, there is unequivocal evidence that there is an elevated risk for suicide attempts in lesbian, gay, or bisexual (LGB) youth above their heterosexual peers. One survey found that 9th-12th grade students who identified as LGB were up to seven times as likely to have a suicide attempt as were their peers who identify as heterosexual. This risk is especially pronounced in male adolescents and continues into adulthood, when there is an elevated risk for suicide completion among adult males who identify as homosexual, although not in adult females (J Homosex. 2011 Jan;58[1]:10-51). Importantly, the risk for suicide attempt in LGB adolescents remains elevated even in those adolescents without any diagnosable mental illness, likely attributable to the stresses of isolation, family conflict, stigmatization, or bullying that LGB adolescents are likely to experience.

Asking your early-adolescent patients in a calm and comfortable manner about sexual feelings builds an environment in which thoughts, feelings, and questions about sex and sexuality are more easily shared. It is important to find language that feels like yours, which you can use with ease. Perhaps starting with, “At about your age, I ask every patient of mine whether they are beginning to have sexual feelings. This is when you really want to be around someone, in a way that’s more powerful and different from even your favorite friend. Some people call it getting butterflies in your stomach.” If your patient recognizes what you are talking about, you might continue, “Do you feel attracted to boys or girls or both? Do you have those feelings about kids in your class or people you know, like a teacher? Perhaps about a celebrity in a TV show or a band?” You should absolutely reassure them, “You don’t have to talk about anything you do not want to, but you should know that this is a normal part of becoming a teenager. I talk about this a lot with patients who are younger and older than you are. I keep what we talk about very private, and sometimes this is the only place a teenager feels safe to ask questions.” If you start this process early enough – by the start of middle school – the patient will probably be a bit embarrassed or giggle and not talk much. But, by the next annual physical or the one after that, the issue will be more familiar and less charged. A meaningful discussion may start.

With patients who do describe feeling attracted to people of the same sex, more specific questions may be appropriate. You should expect these feelings to exist on a continuum: You may encounter a school-age child with great clarity about exactly whom she is attracted to and what that means, or an older teenager who is far less certain, responding to a less intense interest or having been told by a peer that he is probably gay. It can be powerfully reassuring to remind your patient that adolescence is when we start to figure out to whom we are attracted. They don’t have to decide, but just be aware of these feelings as they emerge, essentially getting to know themselves without any feelings of urgency or pressure. You might ask, “Have you wondered if you were gay or bisexual? Have you spoken to any friends about your feelings or have you experimented with a boy or girl to try and figure this out?” It’s very helpful if you ask if they are worried or stressed by these feelings. Some young people will suffer from internalized homophobia, which may be helped by your accepting stance or may require a referral for more ongoing support. It can be valuable to find out if they are dating people of the same sex, or if their “relationships” have all been online. While this “virtual” dating may seem safer, it may not help them better understand themselves and may expose them to exploitation or predatory behavior. If your patient is sexually active, you should be comfortable talking with them about the risks of unprotected sex and same-sex safe-sex practices.

It is particularly important to ask your adolescent LGB patient about whom they have told, and what responses have they gotten. The presence of good friends and loving family members is critical to all adolescents’ emotional well-being. If they have talked about their sexual orientation with their peers, have their friends been supportive, or has it left them more isolated at school? You should find out if they have been teased or bullied, and ask specifically about online teasing or harassment. If they are being bullied, how have they handled that? Find out also if they feel free to ask or talk about this subject with their parents. If not, try to understand if they are simply embarrassed and unsure how to bring it up, or if there is a strong sense that they will be shamed or even rejected by their parents. If the parents are truly shaming or rejecting, it will be critical to consider what kind of support may be necessary. Teens who are facing isolation or bullying at school may benefit from resources such as a gay-straight student alliance or a community organization dedicated to issues facing LGB youth. For patients who are facing hostile or rejecting parents, it can be protective to connect them with a therapist as well, as you are mindful of their marked isolation and subsequently heightened risk for mood problems and even suicide attempts.

Along a similar vein, it is very important that you are aware of your own comfort level with these issues. While discussing sexual orientation may feel awkward if it is new for you, it is important to be realistic if you cannot be supportive of your patients who are gay. If for religious or other reasons you are not comfortable talking about sexual orientation in an accepting, nonjudgmental manner, you should seek guidance on how to thoughtfully care for your LGB patients or appropriately refer them to someone who can provide a more-supportive treatment setting.

When you create an office that makes sexuality a safe topic for discussion, you should expect that you will hear questions or concerns about which you yourself may not know the answers. Do not panic, just maintain your posture of being a curious, compassionate, and nonjudgmental listener, and then look for the answers. We are delighted this news organization has devoted a column to the optimal care of LGBT youth (LGBT Youth Consult) and encourage the primary care pediatrician to “never to worry alone,” and instead get some advice and expert teammates when dealing with these complex and important issues.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, in Newton, Mass. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.

The biological transition to puberty has always marked a critical point in a primary care pediatrician’s relationship to a patient. Adolescents’ capacity for abstract reasoning, their movement to autonomy, their nuanced sense of identity, their need for privacy, and their emerging sexuality together give the pediatrician an opportunity and a responsibility to create a safe place to talk. Your office can be an oasis from parents, peers, and a society that seems saturated with sexuality. You can be trusted more than the Internet and offer discussions that are leavened by your long-standing relationship with the patient.

The growing public awareness, acceptance, and legal standing given to gay, lesbian, bisexual, and transgender individuals represents welcome societal progress, and we sense that amidst this richer public conversation, a growing number of children and adolescents are presenting with questions or worries about their own emerging sexual orientation or gender identity. We would like to start with our key takeaway: Discussions about sexual orientation and gender identity do not require that you give answers or predict the future. Focus instead on being a curious, compassionate, and nonjudgmental listener, and you will be effective at helping your patient to better manage new, uncertain, and possibly stressful feelings.

Our focus today is how to create a safe setting and specifically how to ask about and discuss sexual orientation. Most teenagers will wonder at some point about their orientation. Studies suggest that among adults, 5%-10% are attracted to the same sex and 3% describe themselves as gay or bisexual. Such surveys are very challenging, though, and in our experience, these percentages are higher. Sexual orientation is believed to exist on a continuum rather than in a simple binary state – some people identify as purely homosexual or heterosexual, and the rest exist somewhere in the middle. Sharing this fact alone can offer a very helpful perspective to young people who are feeling pressure to “figure out” if they are gay or straight.

While sexual orientation describes whom a person is attracted to, gender identity is a person’s internal sense of his or her own gender. It emerges in childhood and becomes more rich and nuanced in adolescence and adulthood, and, like sexual orientation, it is also believed to exist on a continuum rather than in a simple binary state. Less than 0.1% of youth will experience gender dysphoria, or the pressing feeling that their gender identity is not the same as their phenotypic sex. While questions about gender identity should be approached with the same curious, compassionate, and nonjudgmental style, we will not discuss the management of patients with gender dysphoria here. It is a very complex (and controversial) topic. And, as a practical matter, sexual orientation will likely be a more common issue with your patients, whereas questions about gender identity will come up much less frequently.

It is worth knowing that there is a range of mental health issues that are associated with the stress of feeling comfortable with one’s sexual identity. There is some evidence that young people who identify as gay or bisexual have elevated risk for mood disorders (depression), anxiety disorders, conduct disorder, and substance use disorders, but this finding has not been consistent (Am J Public Health. 2010:100[12]; 2426-32). However, there is unequivocal evidence that there is an elevated risk for suicide attempts in lesbian, gay, or bisexual (LGB) youth above their heterosexual peers. One survey found that 9th-12th grade students who identified as LGB were up to seven times as likely to have a suicide attempt as were their peers who identify as heterosexual. This risk is especially pronounced in male adolescents and continues into adulthood, when there is an elevated risk for suicide completion among adult males who identify as homosexual, although not in adult females (J Homosex. 2011 Jan;58[1]:10-51). Importantly, the risk for suicide attempt in LGB adolescents remains elevated even in those adolescents without any diagnosable mental illness, likely attributable to the stresses of isolation, family conflict, stigmatization, or bullying that LGB adolescents are likely to experience.

Asking your early-adolescent patients in a calm and comfortable manner about sexual feelings builds an environment in which thoughts, feelings, and questions about sex and sexuality are more easily shared. It is important to find language that feels like yours, which you can use with ease. Perhaps starting with, “At about your age, I ask every patient of mine whether they are beginning to have sexual feelings. This is when you really want to be around someone, in a way that’s more powerful and different from even your favorite friend. Some people call it getting butterflies in your stomach.” If your patient recognizes what you are talking about, you might continue, “Do you feel attracted to boys or girls or both? Do you have those feelings about kids in your class or people you know, like a teacher? Perhaps about a celebrity in a TV show or a band?” You should absolutely reassure them, “You don’t have to talk about anything you do not want to, but you should know that this is a normal part of becoming a teenager. I talk about this a lot with patients who are younger and older than you are. I keep what we talk about very private, and sometimes this is the only place a teenager feels safe to ask questions.” If you start this process early enough – by the start of middle school – the patient will probably be a bit embarrassed or giggle and not talk much. But, by the next annual physical or the one after that, the issue will be more familiar and less charged. A meaningful discussion may start.

With patients who do describe feeling attracted to people of the same sex, more specific questions may be appropriate. You should expect these feelings to exist on a continuum: You may encounter a school-age child with great clarity about exactly whom she is attracted to and what that means, or an older teenager who is far less certain, responding to a less intense interest or having been told by a peer that he is probably gay. It can be powerfully reassuring to remind your patient that adolescence is when we start to figure out to whom we are attracted. They don’t have to decide, but just be aware of these feelings as they emerge, essentially getting to know themselves without any feelings of urgency or pressure. You might ask, “Have you wondered if you were gay or bisexual? Have you spoken to any friends about your feelings or have you experimented with a boy or girl to try and figure this out?” It’s very helpful if you ask if they are worried or stressed by these feelings. Some young people will suffer from internalized homophobia, which may be helped by your accepting stance or may require a referral for more ongoing support. It can be valuable to find out if they are dating people of the same sex, or if their “relationships” have all been online. While this “virtual” dating may seem safer, it may not help them better understand themselves and may expose them to exploitation or predatory behavior. If your patient is sexually active, you should be comfortable talking with them about the risks of unprotected sex and same-sex safe-sex practices.

It is particularly important to ask your adolescent LGB patient about whom they have told, and what responses have they gotten. The presence of good friends and loving family members is critical to all adolescents’ emotional well-being. If they have talked about their sexual orientation with their peers, have their friends been supportive, or has it left them more isolated at school? You should find out if they have been teased or bullied, and ask specifically about online teasing or harassment. If they are being bullied, how have they handled that? Find out also if they feel free to ask or talk about this subject with their parents. If not, try to understand if they are simply embarrassed and unsure how to bring it up, or if there is a strong sense that they will be shamed or even rejected by their parents. If the parents are truly shaming or rejecting, it will be critical to consider what kind of support may be necessary. Teens who are facing isolation or bullying at school may benefit from resources such as a gay-straight student alliance or a community organization dedicated to issues facing LGB youth. For patients who are facing hostile or rejecting parents, it can be protective to connect them with a therapist as well, as you are mindful of their marked isolation and subsequently heightened risk for mood problems and even suicide attempts.

Along a similar vein, it is very important that you are aware of your own comfort level with these issues. While discussing sexual orientation may feel awkward if it is new for you, it is important to be realistic if you cannot be supportive of your patients who are gay. If for religious or other reasons you are not comfortable talking about sexual orientation in an accepting, nonjudgmental manner, you should seek guidance on how to thoughtfully care for your LGB patients or appropriately refer them to someone who can provide a more-supportive treatment setting.

When you create an office that makes sexuality a safe topic for discussion, you should expect that you will hear questions or concerns about which you yourself may not know the answers. Do not panic, just maintain your posture of being a curious, compassionate, and nonjudgmental listener, and then look for the answers. We are delighted this news organization has devoted a column to the optimal care of LGBT youth (LGBT Youth Consult) and encourage the primary care pediatrician to “never to worry alone,” and instead get some advice and expert teammates when dealing with these complex and important issues.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, in Newton, Mass. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.

COPENHAGEN – Back pain is surprisingly common in patients with hidradenitis suppurativa, and more than half of affected patients showed MRI evidence of axial spondyloarthropathy, Dr. Sylke Schneider-Burrus reported at the Annual Congress of the European Academy of Dermatology and Venereology.

“Our study demonstrates that back pain and spondyloarthropathy are very common among hidradenitis suppurativa patients and that neither history nor clinical parameters provide any hints for the presence of spondyloarthropathy. Therefore, we strongly suggest that hidradenitis suppurativa patients should be evaluated for spondyloarthropathy and affected patients should be treated systemically with TNF-alpha blockers in order to avoid chronic joint alterations,” said Dr. Schneider-Burrus, a dermatologist at Charite University Hospital in Berlin.

Bruce Jancin/Frontline Medical News

Hidradenitis suppurativa (HS) is a chronic, recurrent, scarring, inflammatory skin disease of the hair follicles. It causes painful, purulent, foul-smelling fistulating sinuses in the axillae, groin, and perianal region.

Because several other chronic inflammatory diseases affecting epithelial tissue have been associated with increased rates of axial spondyloarthropathy – notably, Crohn’s disease, ulcerative colitis, and psoriasis – Dr. Schneider-Burrus and coinvestigators wondered whether that might true of HS as well.

She presented a survey of 100 HS patients. To her surprise, fully 71% indicated they suffer from back pain, with lower back complaints predominating.

Forty-eight HS patients with back pain consented to undergo a pelvic MRI exam. Fifteen of the 48 (32%) showed clear MRI evidence of spondyloarthropathy, including sacroiliac erosions and subchondral sclerosis, while another 12 showed active sacroiliac synovitis and other acute inflammatory changes.

No significant differences were found between HS patients with and without axial spondyloarthropathy in terms of age at onset of HS, disease duration, HS severity as reflected in Sartorius score, age at MRI, body mass index, or smoking status.

Dr. Schneider-Burrus reported serving as a paid investigator for and consultant to Novartis and AbbVie.

bjancin@frontlinemedcom.com

COPENHAGEN – Back pain is surprisingly common in patients with hidradenitis suppurativa, and more than half of affected patients showed MRI evidence of axial spondyloarthropathy, Dr. Sylke Schneider-Burrus reported at the Annual Congress of the European Academy of Dermatology and Venereology.

“Our study demonstrates that back pain and spondyloarthropathy are very common among hidradenitis suppurativa patients and that neither history nor clinical parameters provide any hints for the presence of spondyloarthropathy. Therefore, we strongly suggest that hidradenitis suppurativa patients should be evaluated for spondyloarthropathy and affected patients should be treated systemically with TNF-alpha blockers in order to avoid chronic joint alterations,” said Dr. Schneider-Burrus, a dermatologist at Charite University Hospital in Berlin.

Bruce Jancin/Frontline Medical News

Hidradenitis suppurativa (HS) is a chronic, recurrent, scarring, inflammatory skin disease of the hair follicles. It causes painful, purulent, foul-smelling fistulating sinuses in the axillae, groin, and perianal region.

Because several other chronic inflammatory diseases affecting epithelial tissue have been associated with increased rates of axial spondyloarthropathy – notably, Crohn’s disease, ulcerative colitis, and psoriasis – Dr. Schneider-Burrus and coinvestigators wondered whether that might true of HS as well.

She presented a survey of 100 HS patients. To her surprise, fully 71% indicated they suffer from back pain, with lower back complaints predominating.

Forty-eight HS patients with back pain consented to undergo a pelvic MRI exam. Fifteen of the 48 (32%) showed clear MRI evidence of spondyloarthropathy, including sacroiliac erosions and subchondral sclerosis, while another 12 showed active sacroiliac synovitis and other acute inflammatory changes.

No significant differences were found between HS patients with and without axial spondyloarthropathy in terms of age at onset of HS, disease duration, HS severity as reflected in Sartorius score, age at MRI, body mass index, or smoking status.

Dr. Schneider-Burrus reported serving as a paid investigator for and consultant to Novartis and AbbVie.

bjancin@frontlinemedcom.com

COPENHAGEN – Back pain is surprisingly common in patients with hidradenitis suppurativa, and more than half of affected patients showed MRI evidence of axial spondyloarthropathy, Dr. Sylke Schneider-Burrus reported at the Annual Congress of the European Academy of Dermatology and Venereology.

“Our study demonstrates that back pain and spondyloarthropathy are very common among hidradenitis suppurativa patients and that neither history nor clinical parameters provide any hints for the presence of spondyloarthropathy. Therefore, we strongly suggest that hidradenitis suppurativa patients should be evaluated for spondyloarthropathy and affected patients should be treated systemically with TNF-alpha blockers in order to avoid chronic joint alterations,” said Dr. Schneider-Burrus, a dermatologist at Charite University Hospital in Berlin.

Bruce Jancin/Frontline Medical News

Hidradenitis suppurativa (HS) is a chronic, recurrent, scarring, inflammatory skin disease of the hair follicles. It causes painful, purulent, foul-smelling fistulating sinuses in the axillae, groin, and perianal region.

Because several other chronic inflammatory diseases affecting epithelial tissue have been associated with increased rates of axial spondyloarthropathy – notably, Crohn’s disease, ulcerative colitis, and psoriasis – Dr. Schneider-Burrus and coinvestigators wondered whether that might true of HS as well.

She presented a survey of 100 HS patients. To her surprise, fully 71% indicated they suffer from back pain, with lower back complaints predominating.

Forty-eight HS patients with back pain consented to undergo a pelvic MRI exam. Fifteen of the 48 (32%) showed clear MRI evidence of spondyloarthropathy, including sacroiliac erosions and subchondral sclerosis, while another 12 showed active sacroiliac synovitis and other acute inflammatory changes.

No significant differences were found between HS patients with and without axial spondyloarthropathy in terms of age at onset of HS, disease duration, HS severity as reflected in Sartorius score, age at MRI, body mass index, or smoking status.

Dr. Schneider-Burrus reported serving as a paid investigator for and consultant to Novartis and AbbVie.

bjancin@frontlinemedcom.com