CHICAGO – The next generation of hybrid carotid stents is slowly breathing life into the stagnant field of carotid artery stenting.

The new hybrid stents combine the flexibility of a traditional open-cell, nitinol stent with the stabilization typically offered by a closed-cell stent design. The initial clinical experience is limited, but shows promising results against embolization, Dr. Claudio Schönholzsaid at a symposium on vascular surgery sponsored by Northwestern University.

Last year, Dr. Schönholz and his colleagues at the Medical University of South Carolina in Charleston reported the first-in-man use of the investigational Gore Carotid Stent (W.L. Gore & Associates) (J. Endovasc. Thera. 2014;21:601-4).

As part of the Gore Carotid Stent Clinical Study for the Treatment of Carotid Artery Stenosis in Patients at Increased Risk for Adverse Events From Carotid Endarterectomy (SCAFFOLD) trial, the team has successfully treated another four patients with no evidence of peri- or postprocedural neurological events. This included a case with such severe high-grade stenosis and slow flow that the external carotid artery was not even visible on imaging before the stent was placed, Dr. Schönholz said.

The Food and Drug Administration recently reviewed unreleased data for the first 100 patients enrolled in SCAFFOLD and given the green light for the multicenter, 312-patient study to resume with the start of the new year, he said.Cristallo study (J. Endovasc. Ther. 2008;15:186-92).

A more recent retrospective study revealed only one minor stroke in the perioperative period and during the first 30 days in 68 patients with symptomatic carotid stenosis treated by Turkish surgeons with the Cristallo Ideale stent and a proximal protection device (MO.MA, Invatec s.r.l., Medtronic, Italy) (Int. Angiol. 2014 Nov. 14. [Epub ahead of print]).

Better patient selection, increased operator experience, and use of embolic protection devices has reduced neurological events associated with carotid artery stenting, but embolization still occurs after protection devices are removed due to plaque protrusion through the stent struts, Dr. Schönholz said. The unique design of the hybrid stents “may prevent plaque protrusion, eliminating peri- and postprocedural events,” he said.The Cristallo Ideale hybrid stent is a nitinol-based stent that has a closed-cell portion at its center and an open-cell configuration on the distal and proximal sections. In contrast, the Gore Carotid Stent has a closed-cell component throughout the entire device length that is created by placing an expanded polytetrafluoroethylene lattice with 500-micrometer pores over an open-cell frame. Once combined, both the stent frame and lattice are coated on all surfaces with Carmeda Bioactive Surface (CBAS) heparin. It’s action is limited only to the device surface and has no systemic anticoagulation effects, said Dr. Schönholz, who disclosed serving on Gore’s scientific advisory board.

The open-cell frame allows a high degree of flexibility and conformity to the native anatomy, while the stent lattice provides a high degree of plaque scaffolding that can reduce plaque prolapse, he said. The lattice also reduces the amount of emboli released during and after stent deployment and stabilizes the stent frame by resisting elongation as well as “fish-scaling,” or the misalignment of stent struts that protrude into the vessel wall, particularly when stents are deployed in tortuous anatomy.

Course director Dr. Mark K. Eskandari, chief of vascular surgery at Northwestern University in Chicago, said the results show that “carotid stenting isn’t dead yet and we can persevere. Advances in technology, both in regards to mechanical embolic protection devices and stent design systems, continue to improve the already great results of carotid artery stenting.”

[email protected]

CHICAGO – The next generation of hybrid carotid stents is slowly breathing life into the stagnant field of carotid artery stenting.

The new hybrid stents combine the flexibility of a traditional open-cell, nitinol stent with the stabilization typically offered by a closed-cell stent design. The initial clinical experience is limited, but shows promising results against embolization, Dr. Claudio Schönholzsaid at a symposium on vascular surgery sponsored by Northwestern University.

Last year, Dr. Schönholz and his colleagues at the Medical University of South Carolina in Charleston reported the first-in-man use of the investigational Gore Carotid Stent (W.L. Gore & Associates) (J. Endovasc. Thera. 2014;21:601-4).

As part of the Gore Carotid Stent Clinical Study for the Treatment of Carotid Artery Stenosis in Patients at Increased Risk for Adverse Events From Carotid Endarterectomy (SCAFFOLD) trial, the team has successfully treated another four patients with no evidence of peri- or postprocedural neurological events. This included a case with such severe high-grade stenosis and slow flow that the external carotid artery was not even visible on imaging before the stent was placed, Dr. Schönholz said.

The Food and Drug Administration recently reviewed unreleased data for the first 100 patients enrolled in SCAFFOLD and given the green light for the multicenter, 312-patient study to resume with the start of the new year, he said.Cristallo study (J. Endovasc. Ther. 2008;15:186-92).

A more recent retrospective study revealed only one minor stroke in the perioperative period and during the first 30 days in 68 patients with symptomatic carotid stenosis treated by Turkish surgeons with the Cristallo Ideale stent and a proximal protection device (MO.MA, Invatec s.r.l., Medtronic, Italy) (Int. Angiol. 2014 Nov. 14. [Epub ahead of print]).

Better patient selection, increased operator experience, and use of embolic protection devices has reduced neurological events associated with carotid artery stenting, but embolization still occurs after protection devices are removed due to plaque protrusion through the stent struts, Dr. Schönholz said. The unique design of the hybrid stents “may prevent plaque protrusion, eliminating peri- and postprocedural events,” he said.The Cristallo Ideale hybrid stent is a nitinol-based stent that has a closed-cell portion at its center and an open-cell configuration on the distal and proximal sections. In contrast, the Gore Carotid Stent has a closed-cell component throughout the entire device length that is created by placing an expanded polytetrafluoroethylene lattice with 500-micrometer pores over an open-cell frame. Once combined, both the stent frame and lattice are coated on all surfaces with Carmeda Bioactive Surface (CBAS) heparin. It’s action is limited only to the device surface and has no systemic anticoagulation effects, said Dr. Schönholz, who disclosed serving on Gore’s scientific advisory board.

The open-cell frame allows a high degree of flexibility and conformity to the native anatomy, while the stent lattice provides a high degree of plaque scaffolding that can reduce plaque prolapse, he said. The lattice also reduces the amount of emboli released during and after stent deployment and stabilizes the stent frame by resisting elongation as well as “fish-scaling,” or the misalignment of stent struts that protrude into the vessel wall, particularly when stents are deployed in tortuous anatomy.

Course director Dr. Mark K. Eskandari, chief of vascular surgery at Northwestern University in Chicago, said the results show that “carotid stenting isn’t dead yet and we can persevere. Advances in technology, both in regards to mechanical embolic protection devices and stent design systems, continue to improve the already great results of carotid artery stenting.”

[email protected]

CHICAGO – The next generation of hybrid carotid stents is slowly breathing life into the stagnant field of carotid artery stenting.

The new hybrid stents combine the flexibility of a traditional open-cell, nitinol stent with the stabilization typically offered by a closed-cell stent design. The initial clinical experience is limited, but shows promising results against embolization, Dr. Claudio Schönholzsaid at a symposium on vascular surgery sponsored by Northwestern University.

Last year, Dr. Schönholz and his colleagues at the Medical University of South Carolina in Charleston reported the first-in-man use of the investigational Gore Carotid Stent (W.L. Gore & Associates) (J. Endovasc. Thera. 2014;21:601-4).

As part of the Gore Carotid Stent Clinical Study for the Treatment of Carotid Artery Stenosis in Patients at Increased Risk for Adverse Events From Carotid Endarterectomy (SCAFFOLD) trial, the team has successfully treated another four patients with no evidence of peri- or postprocedural neurological events. This included a case with such severe high-grade stenosis and slow flow that the external carotid artery was not even visible on imaging before the stent was placed, Dr. Schönholz said.

The Food and Drug Administration recently reviewed unreleased data for the first 100 patients enrolled in SCAFFOLD and given the green light for the multicenter, 312-patient study to resume with the start of the new year, he said.Cristallo study (J. Endovasc. Ther. 2008;15:186-92).

A more recent retrospective study revealed only one minor stroke in the perioperative period and during the first 30 days in 68 patients with symptomatic carotid stenosis treated by Turkish surgeons with the Cristallo Ideale stent and a proximal protection device (MO.MA, Invatec s.r.l., Medtronic, Italy) (Int. Angiol. 2014 Nov. 14. [Epub ahead of print]).

Better patient selection, increased operator experience, and use of embolic protection devices has reduced neurological events associated with carotid artery stenting, but embolization still occurs after protection devices are removed due to plaque protrusion through the stent struts, Dr. Schönholz said. The unique design of the hybrid stents “may prevent plaque protrusion, eliminating peri- and postprocedural events,” he said.The Cristallo Ideale hybrid stent is a nitinol-based stent that has a closed-cell portion at its center and an open-cell configuration on the distal and proximal sections. In contrast, the Gore Carotid Stent has a closed-cell component throughout the entire device length that is created by placing an expanded polytetrafluoroethylene lattice with 500-micrometer pores over an open-cell frame. Once combined, both the stent frame and lattice are coated on all surfaces with Carmeda Bioactive Surface (CBAS) heparin. It’s action is limited only to the device surface and has no systemic anticoagulation effects, said Dr. Schönholz, who disclosed serving on Gore’s scientific advisory board.

The open-cell frame allows a high degree of flexibility and conformity to the native anatomy, while the stent lattice provides a high degree of plaque scaffolding that can reduce plaque prolapse, he said. The lattice also reduces the amount of emboli released during and after stent deployment and stabilizes the stent frame by resisting elongation as well as “fish-scaling,” or the misalignment of stent struts that protrude into the vessel wall, particularly when stents are deployed in tortuous anatomy.

Course director Dr. Mark K. Eskandari, chief of vascular surgery at Northwestern University in Chicago, said the results show that “carotid stenting isn’t dead yet and we can persevere. Advances in technology, both in regards to mechanical embolic protection devices and stent design systems, continue to improve the already great results of carotid artery stenting.”

[email protected]

DNA helices

Image courtesy of NIGMS

Many of the genetic alterations revealed by sequencing a cancer patient’s tumor DNA are not actually associated with the cancer, according to a study published in Science Translational Medicine.

In fact, these alterations are inherited germline mutations already present in an individual’s normal cells.

To make this discovery, researchers compared DNA from tumors and normal cells in 815 patients with hematologic and solid tumor malignancies.

Almost half of the patients analyzed using tumor-only approaches had genetic alterations in their tumors that were also present in their normal cells, which suggests the alterations were “false-positive” changes not specific to the tumor.

As personalized medicine is predicated on tailoring treatments to the genetic makeup of a patient’s tumor, the high rate of false-positives uncovered in this study has implications for the accuracy of the approach when it relies on tumor-only sequencing, the researchers said.

“We knew from our pioneering whole-exome analyses of cancer patients that a significant number of the genetic alterations that were thought to be associated with tumors were also present in the inherited germline DNA,” said Siân Jones, PhD, of Personal Genome Diagnostics in Baltimore, Maryland.

“By comparing tumor DNA to DNA from normal tissue, we were able to separate out those genetic alterations that are truly tumor-specific. Accurately identifying tumor-specific alterations is essential to realizing the potential of personalized medicine to achieve better treatment outcomes.”

The researchers identified 382 genetic alterations that were potentially tumor-specific by first detecting all of the genetic changes in patients’ tumors and then eliminating those that were well-known germline alterations.

However, when the remaining alterations were compared to the genomic profiles of the patients’ germline DNA, an average of 249, or 65%, turned out to be false-positive changes that were already present in the normal cells.

The researchers also looked at the alterations in actionable genes, which have been identified as potential targets for approved or investigational cancer therapies. They found that almost half of the tumor samples (48%) had at least one false-positive mutation in an actionable gene.

The use of false-positive findings to guide personalized treatment decisions could result in a substantial number of patients receiving therapies that are not optimized for their cancer, according to the researchers. Therefore, it seems sequencing normal DNA alongside tumor DNA is essential.

In addition to selecting personalized therapies for cancer patients, sequencing normal DNA can increase the overall understanding of cancer, including finding cancer predisposition due to germline genome changes, said Victor Velculescu, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

In this study, the germline analyses revealed changes in cancer-related genes in 3% of the patients who had no known signs of genetically linked cancer.

“These analyses can help us find alterations in cancer-predisposing genes in ways that weren’t previously appreciated,” Dr Velculescu said.

He also acknowledged, however, that there are challenges to implementing tumor-normal DNA analyses in a clinical setting. These include the additional work and costs of sequencing and analyzing a patient’s normal tissue along with his or her tumor tissue.

Costs for tumor gene sequencing begin at several thousand dollars, which would increase if sequencing was done on DNA from normal tissue as well. And health insurance may not fully cover normal-tissue genetic sequencing.

DNA helices

Image courtesy of NIGMS

Many of the genetic alterations revealed by sequencing a cancer patient’s tumor DNA are not actually associated with the cancer, according to a study published in Science Translational Medicine.

In fact, these alterations are inherited germline mutations already present in an individual’s normal cells.

To make this discovery, researchers compared DNA from tumors and normal cells in 815 patients with hematologic and solid tumor malignancies.

Almost half of the patients analyzed using tumor-only approaches had genetic alterations in their tumors that were also present in their normal cells, which suggests the alterations were “false-positive” changes not specific to the tumor.

As personalized medicine is predicated on tailoring treatments to the genetic makeup of a patient’s tumor, the high rate of false-positives uncovered in this study has implications for the accuracy of the approach when it relies on tumor-only sequencing, the researchers said.

“We knew from our pioneering whole-exome analyses of cancer patients that a significant number of the genetic alterations that were thought to be associated with tumors were also present in the inherited germline DNA,” said Siân Jones, PhD, of Personal Genome Diagnostics in Baltimore, Maryland.

“By comparing tumor DNA to DNA from normal tissue, we were able to separate out those genetic alterations that are truly tumor-specific. Accurately identifying tumor-specific alterations is essential to realizing the potential of personalized medicine to achieve better treatment outcomes.”

The researchers identified 382 genetic alterations that were potentially tumor-specific by first detecting all of the genetic changes in patients’ tumors and then eliminating those that were well-known germline alterations.

However, when the remaining alterations were compared to the genomic profiles of the patients’ germline DNA, an average of 249, or 65%, turned out to be false-positive changes that were already present in the normal cells.

The researchers also looked at the alterations in actionable genes, which have been identified as potential targets for approved or investigational cancer therapies. They found that almost half of the tumor samples (48%) had at least one false-positive mutation in an actionable gene.

The use of false-positive findings to guide personalized treatment decisions could result in a substantial number of patients receiving therapies that are not optimized for their cancer, according to the researchers. Therefore, it seems sequencing normal DNA alongside tumor DNA is essential.

In addition to selecting personalized therapies for cancer patients, sequencing normal DNA can increase the overall understanding of cancer, including finding cancer predisposition due to germline genome changes, said Victor Velculescu, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

In this study, the germline analyses revealed changes in cancer-related genes in 3% of the patients who had no known signs of genetically linked cancer.

“These analyses can help us find alterations in cancer-predisposing genes in ways that weren’t previously appreciated,” Dr Velculescu said.

He also acknowledged, however, that there are challenges to implementing tumor-normal DNA analyses in a clinical setting. These include the additional work and costs of sequencing and analyzing a patient’s normal tissue along with his or her tumor tissue.

Costs for tumor gene sequencing begin at several thousand dollars, which would increase if sequencing was done on DNA from normal tissue as well. And health insurance may not fully cover normal-tissue genetic sequencing.

DNA helices

Image courtesy of NIGMS

Many of the genetic alterations revealed by sequencing a cancer patient’s tumor DNA are not actually associated with the cancer, according to a study published in Science Translational Medicine.

In fact, these alterations are inherited germline mutations already present in an individual’s normal cells.

To make this discovery, researchers compared DNA from tumors and normal cells in 815 patients with hematologic and solid tumor malignancies.

Almost half of the patients analyzed using tumor-only approaches had genetic alterations in their tumors that were also present in their normal cells, which suggests the alterations were “false-positive” changes not specific to the tumor.

As personalized medicine is predicated on tailoring treatments to the genetic makeup of a patient’s tumor, the high rate of false-positives uncovered in this study has implications for the accuracy of the approach when it relies on tumor-only sequencing, the researchers said.

“We knew from our pioneering whole-exome analyses of cancer patients that a significant number of the genetic alterations that were thought to be associated with tumors were also present in the inherited germline DNA,” said Siân Jones, PhD, of Personal Genome Diagnostics in Baltimore, Maryland.

“By comparing tumor DNA to DNA from normal tissue, we were able to separate out those genetic alterations that are truly tumor-specific. Accurately identifying tumor-specific alterations is essential to realizing the potential of personalized medicine to achieve better treatment outcomes.”

The researchers identified 382 genetic alterations that were potentially tumor-specific by first detecting all of the genetic changes in patients’ tumors and then eliminating those that were well-known germline alterations.

However, when the remaining alterations were compared to the genomic profiles of the patients’ germline DNA, an average of 249, or 65%, turned out to be false-positive changes that were already present in the normal cells.

The researchers also looked at the alterations in actionable genes, which have been identified as potential targets for approved or investigational cancer therapies. They found that almost half of the tumor samples (48%) had at least one false-positive mutation in an actionable gene.

The use of false-positive findings to guide personalized treatment decisions could result in a substantial number of patients receiving therapies that are not optimized for their cancer, according to the researchers. Therefore, it seems sequencing normal DNA alongside tumor DNA is essential.

In addition to selecting personalized therapies for cancer patients, sequencing normal DNA can increase the overall understanding of cancer, including finding cancer predisposition due to germline genome changes, said Victor Velculescu, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

In this study, the germline analyses revealed changes in cancer-related genes in 3% of the patients who had no known signs of genetically linked cancer.

“These analyses can help us find alterations in cancer-predisposing genes in ways that weren’t previously appreciated,” Dr Velculescu said.

He also acknowledged, however, that there are challenges to implementing tumor-normal DNA analyses in a clinical setting. These include the additional work and costs of sequencing and analyzing a patient’s normal tissue along with his or her tumor tissue.

Costs for tumor gene sequencing begin at several thousand dollars, which would increase if sequencing was done on DNA from normal tissue as well. And health insurance may not fully cover normal-tissue genetic sequencing.

Researcher in the lab

Photo by Darren Baker

A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.

The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.

It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.

So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.

“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.

“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”

With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.

The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.

When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.

In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.

The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.

“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.

“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”

To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.

Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype.  And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).

“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”

Researcher in the lab

Photo by Darren Baker

A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.

The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.

It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.

So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.

“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.

“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”

With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.

The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.

When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.

In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.

The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.

“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.

“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”

To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.

Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype.  And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).

“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”

Researcher in the lab

Photo by Darren Baker

A new technique can quickly and easily differentiate the two major subtypes of diffuse large B-cell lymphoma (DLBCL), researchers have reported in The Journal of Molecular Diagnostics.

The method is based on a reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay and 14 gene signatures.

It proved as accurate as the gold standard technology for identifying germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL.

So the researchers believe this RT-MLPA-based assay could help clinicians evaluate a patient’s prognosis and choose the optimal therapy for a person with DLBCL.

“Differences in the progression of the disease and clinical outcomes can, at least in part, be explained by the heterogeneity of lymphoma, which can be classified into two major subtypes with different outcomes,” said study author Philippe Ruminy, PhD, of the University of Rouen in France.

“Unfortunately, these lymphomas are morphologically undistinguishable in routine diagnosis, which is a major problem for the development of targeted therapies. Furthermore, array-based gene expression profiling (GEP), which is considered the gold standard for discriminating these tumors, remains poorly transposable to routine diagnosis, and the surrogate immunohistochemical (IHC) algorithms that have been proposed are often considered poorly reliable.”

With this in mind, Dr Ruminy and his colleagues tested the RT-MLPA-based assay alongside GEP techniques in samples from 259 patients with de novo DLBCL.

The team used a series of 195 patients from a single institution to train and validate the new technique. Of these patients, 115 had a classification determined with a Veracode DASL assay, 100 had an IHC classification, and 135 had survival data. A second series of 64 patients that were previously analyzed by Affymetrix U133+2 GEP arrays served as an external validation cohort.

When the researchers looked at 50 patients randomly selected from the training cohort, they found that the RT-MLPA-based assay classified 90% of the cases within the expected subtypes (20 GCB and 25 ABC). The remaining 10% (1 GCB and 4 ABC) were considered unclassified.

In the external validation cohort, the RT-MLPA-based assay classified 80% of cases within the expected subtypes (24 ABC and 28 GCB). However, 13.8% were considered unclassified (3 GCB and 6 ABC), and 4 were misclassified.

The researchers also found the RT-MLPA-based assay was sensitive for analyzing archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. A comparison of samples from paired frozen and FFPE biopsies showed that the technique correctly classified 89.3% of 28 cases.

“Because RT-MLPA requires only short cDNA fragments for the correct binding and ligation of the gene-specific oligonucleotide probes, it is less affected by the use of low RNA concentrations and RNA degradation,” Dr Ruminy said.

“It could thus be used for the retrospective analysis of archival collections and for the inclusion of patients in prospective clinical trials, because only a few institutions routinely collect frozen biopsy material.”

To evaluate the prognostic value of the assay, the researchers looked at survival in 135 treated DLBCL patients who were diagnosed between 2001 and 2011.

Patients determined to have the ABC subtype by the RT-MLPA-based assay had significantly worse progression-free survival and overall survival than patients with the GCB subtype.  And the expression of several individual genes within the MLPA signature was significantly associated with prognosis (ie, high LMO2, high BCL6, and low TNFRSF13B expression).

“The robust and cost-effective RT-MLPA assay can yield results within one day and requires reagents costing less than $5 per sample,” Dr Ruminy said. “Since RT-MLPA utilizes materials and equipment that are standard in many laboratories, the process can easily be implemented for routine use.”

A macrophage stretching its

pseudopodia to engulf particles

Macrophages can substitute for dendritic cells as primers of T-cell-dependent immune responses, according to research published in Proceedings of the National Academy of Sciences.

The study showed that macrophages that function as a first line of defense in the innate immune system can also present antigens to T cells, a previously unknown role for macrophages in the induction of adaptive immune responses.

“It has been assumed until now that the dendritic cells are considered to be essentially the only cell type responsible for antigen presentation in the immune system,” said Dr Thomas Brocker, of Ludwig-Maximilians-Universität München in Germany.

“We have now discovered that macrophages can also do this job. Not only that, in certain situations, they can be more effective than dendritic cells.”

Dendritic cells present antigens to cytotoxic T lymphocytes (CTLs) if they have been directly infected, but they can also capture and display antigens from other cells. This type of indirect antigen presentation is referred to as cross-presentation.

“So, theoretically, dendritic cells could be responsible for the induction of all CTL-based responses, regardless of whether they are themselves infected or not,” Dr Brocker said. “But the significance of cross-presentation is hotly debated in the literature.”

Dr Brocker and his team used several antigens that were specifically targeted to and processed by macrophages but could not be taken up directly by dendritic cells. They were able to demonstrate that each antigen induced a normal immune response in a mouse model system, and even in a mouse strain that lacked dendritic cells altogether.

Further experiments showed the targeted macrophages were actually able to prime a more comprehensive immune reaction than cross-presenting dendritic cells. They activated T cells specific for all antigen-binding sites (epitopes) presented, whereas cross-presentation by dendritic cells stimulates only those T cells that recognize immunodominant epitopes.

“Macrophages naturally function as filters,” Dr Brocker noted. “They gobble everything up that might be harmful to the organism. And our study shows that, in contrast to cross-priming dendritic cells, they are capable of producing and presenting all T-cell-priming epitopes we tested. Macrophages therefore induce a complete immune response. These observations indicate that the significance of cross-presentation by dendritic cells has been overrated.”

He added that these findings are relevant for the development of immunization strategies.

“Preclinical trials are already underway with vaccines that are designed to activate specific sets of dendritic cells,” Dr Brocker said. “But the weak epitopes are important for a broadly directed immune response, because they can potentially recognize mutant variants of viruses, for instance.”

“Cross-priming dendritic cells fail to induce weakly antigenic epitopes, as our study shows. Our results indicate that it may make more sense to manipulate macrophages directly because they stimulate a wider-ranging immune response.”

A macrophage stretching its

pseudopodia to engulf particles

Macrophages can substitute for dendritic cells as primers of T-cell-dependent immune responses, according to research published in Proceedings of the National Academy of Sciences.

The study showed that macrophages that function as a first line of defense in the innate immune system can also present antigens to T cells, a previously unknown role for macrophages in the induction of adaptive immune responses.

“It has been assumed until now that the dendritic cells are considered to be essentially the only cell type responsible for antigen presentation in the immune system,” said Dr Thomas Brocker, of Ludwig-Maximilians-Universität München in Germany.

“We have now discovered that macrophages can also do this job. Not only that, in certain situations, they can be more effective than dendritic cells.”

Dendritic cells present antigens to cytotoxic T lymphocytes (CTLs) if they have been directly infected, but they can also capture and display antigens from other cells. This type of indirect antigen presentation is referred to as cross-presentation.

“So, theoretically, dendritic cells could be responsible for the induction of all CTL-based responses, regardless of whether they are themselves infected or not,” Dr Brocker said. “But the significance of cross-presentation is hotly debated in the literature.”

Dr Brocker and his team used several antigens that were specifically targeted to and processed by macrophages but could not be taken up directly by dendritic cells. They were able to demonstrate that each antigen induced a normal immune response in a mouse model system, and even in a mouse strain that lacked dendritic cells altogether.

Further experiments showed the targeted macrophages were actually able to prime a more comprehensive immune reaction than cross-presenting dendritic cells. They activated T cells specific for all antigen-binding sites (epitopes) presented, whereas cross-presentation by dendritic cells stimulates only those T cells that recognize immunodominant epitopes.

“Macrophages naturally function as filters,” Dr Brocker noted. “They gobble everything up that might be harmful to the organism. And our study shows that, in contrast to cross-priming dendritic cells, they are capable of producing and presenting all T-cell-priming epitopes we tested. Macrophages therefore induce a complete immune response. These observations indicate that the significance of cross-presentation by dendritic cells has been overrated.”

He added that these findings are relevant for the development of immunization strategies.

“Preclinical trials are already underway with vaccines that are designed to activate specific sets of dendritic cells,” Dr Brocker said. “But the weak epitopes are important for a broadly directed immune response, because they can potentially recognize mutant variants of viruses, for instance.”

“Cross-priming dendritic cells fail to induce weakly antigenic epitopes, as our study shows. Our results indicate that it may make more sense to manipulate macrophages directly because they stimulate a wider-ranging immune response.”

A macrophage stretching its

pseudopodia to engulf particles

Macrophages can substitute for dendritic cells as primers of T-cell-dependent immune responses, according to research published in Proceedings of the National Academy of Sciences.

The study showed that macrophages that function as a first line of defense in the innate immune system can also present antigens to T cells, a previously unknown role for macrophages in the induction of adaptive immune responses.

“It has been assumed until now that the dendritic cells are considered to be essentially the only cell type responsible for antigen presentation in the immune system,” said Dr Thomas Brocker, of Ludwig-Maximilians-Universität München in Germany.

“We have now discovered that macrophages can also do this job. Not only that, in certain situations, they can be more effective than dendritic cells.”

Dendritic cells present antigens to cytotoxic T lymphocytes (CTLs) if they have been directly infected, but they can also capture and display antigens from other cells. This type of indirect antigen presentation is referred to as cross-presentation.

“So, theoretically, dendritic cells could be responsible for the induction of all CTL-based responses, regardless of whether they are themselves infected or not,” Dr Brocker said. “But the significance of cross-presentation is hotly debated in the literature.”

Dr Brocker and his team used several antigens that were specifically targeted to and processed by macrophages but could not be taken up directly by dendritic cells. They were able to demonstrate that each antigen induced a normal immune response in a mouse model system, and even in a mouse strain that lacked dendritic cells altogether.

Further experiments showed the targeted macrophages were actually able to prime a more comprehensive immune reaction than cross-presenting dendritic cells. They activated T cells specific for all antigen-binding sites (epitopes) presented, whereas cross-presentation by dendritic cells stimulates only those T cells that recognize immunodominant epitopes.

“Macrophages naturally function as filters,” Dr Brocker noted. “They gobble everything up that might be harmful to the organism. And our study shows that, in contrast to cross-priming dendritic cells, they are capable of producing and presenting all T-cell-priming epitopes we tested. Macrophages therefore induce a complete immune response. These observations indicate that the significance of cross-presentation by dendritic cells has been overrated.”

He added that these findings are relevant for the development of immunization strategies.

“Preclinical trials are already underway with vaccines that are designed to activate specific sets of dendritic cells,” Dr Brocker said. “But the weak epitopes are important for a broadly directed immune response, because they can potentially recognize mutant variants of viruses, for instance.”

“Cross-priming dendritic cells fail to induce weakly antigenic epitopes, as our study shows. Our results indicate that it may make more sense to manipulate macrophages directly because they stimulate a wider-ranging immune response.”

Pregnant woman

Photo by Nina Matthews

The Royal College of Obstetricians and Gynaecologists (RCOG) has released new guidelines for treating and preventing venous thromboembolism (VTE) during pregnancy, birth, and following delivery.

“These updated guidelines provide new evidence about risk factors for thrombosis in pregnancy and strategies that should be employed to reduce the chances of a thrombosis occurring,” said Andrew Thomson, MD, cochair of the RCOG guidelines committee.

“Furthermore, the guidelines provide updated information on the way women with a suspected thrombosis should be investigated and treated.”

VTE is uncommon in pregnancy or in the first 6 weeks postnatally, and the absolute risk of VTE is around 1 in 1000 pregnancies. It can occur at any stage in pregnancy, but the time of the highest risk is the first 6 weeks following birth, when the risk increases 20-fold.

Risk factors include previous VTE or thrombophilia, obesity, increased maternal age, immobility and long-distance travel, admission to hospital during pregnancy, and other comorbidities such as heart disease, inflammatory bowel disease, and pre-eclampsia.

Additional risk factors occurring during the first trimester of pregnancy include hyperemesis gravidarum, ovarian hyperstimulation, and in vitro fertilization pregnancy. Caesarean section is also a risk factor.

The guidelines emphasize that all women should undergo a thorough assessment for VTE in early pregnancy or prepregnancy and again intrapartum or immediately postpartum.

Any woman with risk factors should be considered for prophylactic low-molecular-weight heparin. The duration of treatment depends on the number of risk factors a woman has. It may be offered both antenatally and after the baby is born.

In addition, women with previous VTE must be offered prepregnancy counseling. A prospective management plan for VTE should also be made, including appropriate treatment to be offered as early as possible and a careful history documented.

The guidance on treating VTE focuses on the acute management of the condition and highlights the signs and symptoms, including leg pain and swelling, lower abdominal pain, shortness of breath, chest pain, coughing blood, and collapse.

Any woman presenting with signs and symptoms suggestive of VTE should be tested for the condition immediately and offered treatment with low-molecular-weight heparin.

All hospitals should have a protocol for the diagnosis of suspected VTE, with the involvement of a multidisciplinary team of obstetricians, radiologists, physicians, and hematologists.

“This guidance provides clinicians with accurate, scientific-based guidelines on the risk factors for VTE, as well as on how to prevent and treat the condition,” said guideline author Catherine Nelson-Piercy, MBBS, of Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.

“It is vital that VTE is discussed with all women who are at risk, and the reasons for individual treatment recommendations must also be explained.”

Pregnant woman

Photo by Nina Matthews

The Royal College of Obstetricians and Gynaecologists (RCOG) has released new guidelines for treating and preventing venous thromboembolism (VTE) during pregnancy, birth, and following delivery.

“These updated guidelines provide new evidence about risk factors for thrombosis in pregnancy and strategies that should be employed to reduce the chances of a thrombosis occurring,” said Andrew Thomson, MD, cochair of the RCOG guidelines committee.

“Furthermore, the guidelines provide updated information on the way women with a suspected thrombosis should be investigated and treated.”

VTE is uncommon in pregnancy or in the first 6 weeks postnatally, and the absolute risk of VTE is around 1 in 1000 pregnancies. It can occur at any stage in pregnancy, but the time of the highest risk is the first 6 weeks following birth, when the risk increases 20-fold.

Risk factors include previous VTE or thrombophilia, obesity, increased maternal age, immobility and long-distance travel, admission to hospital during pregnancy, and other comorbidities such as heart disease, inflammatory bowel disease, and pre-eclampsia.

Additional risk factors occurring during the first trimester of pregnancy include hyperemesis gravidarum, ovarian hyperstimulation, and in vitro fertilization pregnancy. Caesarean section is also a risk factor.

The guidelines emphasize that all women should undergo a thorough assessment for VTE in early pregnancy or prepregnancy and again intrapartum or immediately postpartum.

Any woman with risk factors should be considered for prophylactic low-molecular-weight heparin. The duration of treatment depends on the number of risk factors a woman has. It may be offered both antenatally and after the baby is born.

In addition, women with previous VTE must be offered prepregnancy counseling. A prospective management plan for VTE should also be made, including appropriate treatment to be offered as early as possible and a careful history documented.

The guidance on treating VTE focuses on the acute management of the condition and highlights the signs and symptoms, including leg pain and swelling, lower abdominal pain, shortness of breath, chest pain, coughing blood, and collapse.

Any woman presenting with signs and symptoms suggestive of VTE should be tested for the condition immediately and offered treatment with low-molecular-weight heparin.

All hospitals should have a protocol for the diagnosis of suspected VTE, with the involvement of a multidisciplinary team of obstetricians, radiologists, physicians, and hematologists.

“This guidance provides clinicians with accurate, scientific-based guidelines on the risk factors for VTE, as well as on how to prevent and treat the condition,” said guideline author Catherine Nelson-Piercy, MBBS, of Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.

“It is vital that VTE is discussed with all women who are at risk, and the reasons for individual treatment recommendations must also be explained.”

Pregnant woman

Photo by Nina Matthews

The Royal College of Obstetricians and Gynaecologists (RCOG) has released new guidelines for treating and preventing venous thromboembolism (VTE) during pregnancy, birth, and following delivery.

“These updated guidelines provide new evidence about risk factors for thrombosis in pregnancy and strategies that should be employed to reduce the chances of a thrombosis occurring,” said Andrew Thomson, MD, cochair of the RCOG guidelines committee.

“Furthermore, the guidelines provide updated information on the way women with a suspected thrombosis should be investigated and treated.”

VTE is uncommon in pregnancy or in the first 6 weeks postnatally, and the absolute risk of VTE is around 1 in 1000 pregnancies. It can occur at any stage in pregnancy, but the time of the highest risk is the first 6 weeks following birth, when the risk increases 20-fold.

Risk factors include previous VTE or thrombophilia, obesity, increased maternal age, immobility and long-distance travel, admission to hospital during pregnancy, and other comorbidities such as heart disease, inflammatory bowel disease, and pre-eclampsia.

Additional risk factors occurring during the first trimester of pregnancy include hyperemesis gravidarum, ovarian hyperstimulation, and in vitro fertilization pregnancy. Caesarean section is also a risk factor.

The guidelines emphasize that all women should undergo a thorough assessment for VTE in early pregnancy or prepregnancy and again intrapartum or immediately postpartum.

Any woman with risk factors should be considered for prophylactic low-molecular-weight heparin. The duration of treatment depends on the number of risk factors a woman has. It may be offered both antenatally and after the baby is born.

In addition, women with previous VTE must be offered prepregnancy counseling. A prospective management plan for VTE should also be made, including appropriate treatment to be offered as early as possible and a careful history documented.

The guidance on treating VTE focuses on the acute management of the condition and highlights the signs and symptoms, including leg pain and swelling, lower abdominal pain, shortness of breath, chest pain, coughing blood, and collapse.

Any woman presenting with signs and symptoms suggestive of VTE should be tested for the condition immediately and offered treatment with low-molecular-weight heparin.

All hospitals should have a protocol for the diagnosis of suspected VTE, with the involvement of a multidisciplinary team of obstetricians, radiologists, physicians, and hematologists.

“This guidance provides clinicians with accurate, scientific-based guidelines on the risk factors for VTE, as well as on how to prevent and treat the condition,” said guideline author Catherine Nelson-Piercy, MBBS, of Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.

“It is vital that VTE is discussed with all women who are at risk, and the reasons for individual treatment recommendations must also be explained.”

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

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

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

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

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

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

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

Obstetric providers are being called upon to care for an increasing number of cancer survivors. Whether it was a childhood cancer or one faced in early adulthood, pregnant cancer survivors raise a unique set of questions and concerns. A general knowledge about management is essential in counseling these women prior to and early in pregnancy.

For the woman who presents preconception, one of the most common questions is when is the best time for pregnancy. Importantly, there are no absolute guidelines on how long a woman should be “disease free.” Many providers suggest waiting 2 years from the time of diagnosis. This “conventional wisdom” is not based on evidence (Oncology 2005;19:693-7). Instead, the type of cancer and the length of treatment can help determine the answer.

Many oncologists prefer a specific time for monitoring after treatment to ensure that initial treatment has been successful. For example, in the case of melanoma, after 2 years, the estimate of recurrence risk may be more accurate (Cancer Causes Control 2008;19:437-42). After breast cancer, women are often followed with MRI with contrast and mammogram. Since both are problematic in pregnancy, 3-5 years may be more appropriate.

Many patients are concerned about the risk of recurrence during pregnancy. Though data are limited, pregnancy does not appear to increase the risk of disease recurrence or decrease disease-free survival, even in the case of more aggressive cancers such as melanoma. This remains true in the setting of hormone receptor–positive cancers, specifically breast cancer (Lancet 1997;350:319-22).

Preconception counseling

The risks for a cancer survivor during pregnancy will vary depending on the treatments she has received. Preconception evaluation should be modified for the specific oncologic therapies. For example, women who received chest radiation, or anthracycline-based chemotherapies (or any cardiotoxic medications) should have a cardiac evaluation as they are at risk of cardiac dysfunction prior to and during pregnancy (Matern. Child. Health J. 2006;10[suppl. 1]:165-8).

Additionally, because chemotherapy may be hepatotoxic or nephrotoxic, baseline liver and renal function tests should almost always be performed. It is not unreasonable to follow these during pregnancy given the physiologic changes.

Many women also are concerned about the risks that prior cancer therapies may have for their baby. Prior chemotherapy and radiation therapy do not appear to confer any increased risk for genetic conditions, anomalies, or childhood cancer (Am. J. Obstet. Gynecol. 2002;187:1070-80). Additionally, previous chemotherapy alone does not increase the risk of adverse pregnancy outcomes.

In contrast, prior radiation to the abdomen and pelvis has been associated with an increased risk of miscarriage, growth restriction, preterm delivery, and stillbirth (J. Natl. Cancer Instit. Monogr. 2005;34:64-8; Lancet 2010;376:624-30). There is an increased risk of cancer in the offspring of women whose cancer is the result of hereditary cancer syndromes, such as BRCA or hereditary nonpolyposis colorectal cancer. Discussions with a genetics counselor may be helpful if there are any questions related to these syndromes.

Pregnancy management

Once pregnant, management requires a multidisciplinary approach. Surveillance options are limited during pregnancy. CT should be avoided, and radiographs limited. Ultrasound of the abdomen is safe, but optimal images are often obscured in later trimesters. Ultimately, indicated imaging should not be forsaken if there are any signs or symptoms that raise concerns for recurrence. Additionally, many tumor markers may be unreliable during pregnancy, such as CA-125 in the first trimester, or alpha-FP and CEA anytime.

Specific recommendations for antenatal testing do not exist and should be assessed on a case-by-case basis; especially in the case of women who have had prior radiation therapy. Our recommendation is to perform growth surveillance, which may include sonography at varying intervals. Also consider weekly fetal testing from 32 weeks in normally growing fetuses.

Solely being a cancer survivor is not an indication for early delivery or induction of labor. In the majority of cases, mode of delivery should be guided by obstetric indications, though previous pelvic surgery and reconstruction may be indications for cesarean delivery. Despite being in remission, some cancers metastasize to the placenta, most commonly melanoma and hematologic cancers. Very rarely, these cancers can also metastasize to the fetus. Thus, the placenta should be sent for histologic evaluation, with a notation to the pathologist about the patient’s prior cancer (Obstet. Gynecol. Surv. 1989;44:535-40; Ultrasound. Obstet. Gynecol. 2009;33:235-44).

In most cases, pregnancy after cancer is uncomplicated with good outcomes for both mother and baby. However, there are potential medical and obstetric complications that cannot be overlooked. Interdisciplinary management is crucial to ensure a safe transition from cancer survivor to mother.

What to consider when counseling cancer survivors about pregnancy

• The recommended disease-free interval prior to pregnancy may vary by cancer type, and is largely driven by disease surveillance needs and recurrence intervals.

• Prior cancer, associated operations, and chemotherapies do not typically confer additional risks in pregnancy. Exceptions include melanoma and blood cell cancers, which may metastasize to the placenta and fetus, even following periods of remission.

• Radiation therapy to the abdomen and pelvis may induce changes that predispose to growth restriction, preterm birth, and stillbirth. Enhanced surveillance may be reasonable in these cases.

• Preconception or early pregnancy assessment for end organ dysfunction is recommended for women who have received certain therapies: cardiac evaluation following chest radiation or anthracycline-based therapy; liver and kidney function for most chemotherapies.

Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal and child health at the University of North Carolina at Chapel Hill. Dr. Dotters-Katz is a maternal-fetal medicine fellow at University of North Carolina at Chapel Hill, who completed her ob.gyn. residency at Duke University. Her academic interests include oncology and infectious diseases as they relate to pregnancy. The authors reported having no financial disclosures. Email them at [email protected].

Obstetric providers are being called upon to care for an increasing number of cancer survivors. Whether it was a childhood cancer or one faced in early adulthood, pregnant cancer survivors raise a unique set of questions and concerns. A general knowledge about management is essential in counseling these women prior to and early in pregnancy.

For the woman who presents preconception, one of the most common questions is when is the best time for pregnancy. Importantly, there are no absolute guidelines on how long a woman should be “disease free.” Many providers suggest waiting 2 years from the time of diagnosis. This “conventional wisdom” is not based on evidence (Oncology 2005;19:693-7). Instead, the type of cancer and the length of treatment can help determine the answer.

Many oncologists prefer a specific time for monitoring after treatment to ensure that initial treatment has been successful. For example, in the case of melanoma, after 2 years, the estimate of recurrence risk may be more accurate (Cancer Causes Control 2008;19:437-42). After breast cancer, women are often followed with MRI with contrast and mammogram. Since both are problematic in pregnancy, 3-5 years may be more appropriate.

Many patients are concerned about the risk of recurrence during pregnancy. Though data are limited, pregnancy does not appear to increase the risk of disease recurrence or decrease disease-free survival, even in the case of more aggressive cancers such as melanoma. This remains true in the setting of hormone receptor–positive cancers, specifically breast cancer (Lancet 1997;350:319-22).

Preconception counseling

The risks for a cancer survivor during pregnancy will vary depending on the treatments she has received. Preconception evaluation should be modified for the specific oncologic therapies. For example, women who received chest radiation, or anthracycline-based chemotherapies (or any cardiotoxic medications) should have a cardiac evaluation as they are at risk of cardiac dysfunction prior to and during pregnancy (Matern. Child. Health J. 2006;10[suppl. 1]:165-8).

Additionally, because chemotherapy may be hepatotoxic or nephrotoxic, baseline liver and renal function tests should almost always be performed. It is not unreasonable to follow these during pregnancy given the physiologic changes.

Many women also are concerned about the risks that prior cancer therapies may have for their baby. Prior chemotherapy and radiation therapy do not appear to confer any increased risk for genetic conditions, anomalies, or childhood cancer (Am. J. Obstet. Gynecol. 2002;187:1070-80). Additionally, previous chemotherapy alone does not increase the risk of adverse pregnancy outcomes.

In contrast, prior radiation to the abdomen and pelvis has been associated with an increased risk of miscarriage, growth restriction, preterm delivery, and stillbirth (J. Natl. Cancer Instit. Monogr. 2005;34:64-8; Lancet 2010;376:624-30). There is an increased risk of cancer in the offspring of women whose cancer is the result of hereditary cancer syndromes, such as BRCA or hereditary nonpolyposis colorectal cancer. Discussions with a genetics counselor may be helpful if there are any questions related to these syndromes.

Pregnancy management

Once pregnant, management requires a multidisciplinary approach. Surveillance options are limited during pregnancy. CT should be avoided, and radiographs limited. Ultrasound of the abdomen is safe, but optimal images are often obscured in later trimesters. Ultimately, indicated imaging should not be forsaken if there are any signs or symptoms that raise concerns for recurrence. Additionally, many tumor markers may be unreliable during pregnancy, such as CA-125 in the first trimester, or alpha-FP and CEA anytime.

Specific recommendations for antenatal testing do not exist and should be assessed on a case-by-case basis; especially in the case of women who have had prior radiation therapy. Our recommendation is to perform growth surveillance, which may include sonography at varying intervals. Also consider weekly fetal testing from 32 weeks in normally growing fetuses.

Solely being a cancer survivor is not an indication for early delivery or induction of labor. In the majority of cases, mode of delivery should be guided by obstetric indications, though previous pelvic surgery and reconstruction may be indications for cesarean delivery. Despite being in remission, some cancers metastasize to the placenta, most commonly melanoma and hematologic cancers. Very rarely, these cancers can also metastasize to the fetus. Thus, the placenta should be sent for histologic evaluation, with a notation to the pathologist about the patient’s prior cancer (Obstet. Gynecol. Surv. 1989;44:535-40; Ultrasound. Obstet. Gynecol. 2009;33:235-44).

In most cases, pregnancy after cancer is uncomplicated with good outcomes for both mother and baby. However, there are potential medical and obstetric complications that cannot be overlooked. Interdisciplinary management is crucial to ensure a safe transition from cancer survivor to mother.

What to consider when counseling cancer survivors about pregnancy

• The recommended disease-free interval prior to pregnancy may vary by cancer type, and is largely driven by disease surveillance needs and recurrence intervals.

• Prior cancer, associated operations, and chemotherapies do not typically confer additional risks in pregnancy. Exceptions include melanoma and blood cell cancers, which may metastasize to the placenta and fetus, even following periods of remission.

• Radiation therapy to the abdomen and pelvis may induce changes that predispose to growth restriction, preterm birth, and stillbirth. Enhanced surveillance may be reasonable in these cases.

• Preconception or early pregnancy assessment for end organ dysfunction is recommended for women who have received certain therapies: cardiac evaluation following chest radiation or anthracycline-based therapy; liver and kidney function for most chemotherapies.

Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal and child health at the University of North Carolina at Chapel Hill. Dr. Dotters-Katz is a maternal-fetal medicine fellow at University of North Carolina at Chapel Hill, who completed her ob.gyn. residency at Duke University. Her academic interests include oncology and infectious diseases as they relate to pregnancy. The authors reported having no financial disclosures. Email them at [email protected].

Obstetric providers are being called upon to care for an increasing number of cancer survivors. Whether it was a childhood cancer or one faced in early adulthood, pregnant cancer survivors raise a unique set of questions and concerns. A general knowledge about management is essential in counseling these women prior to and early in pregnancy.

For the woman who presents preconception, one of the most common questions is when is the best time for pregnancy. Importantly, there are no absolute guidelines on how long a woman should be “disease free.” Many providers suggest waiting 2 years from the time of diagnosis. This “conventional wisdom” is not based on evidence (Oncology 2005;19:693-7). Instead, the type of cancer and the length of treatment can help determine the answer.

Many oncologists prefer a specific time for monitoring after treatment to ensure that initial treatment has been successful. For example, in the case of melanoma, after 2 years, the estimate of recurrence risk may be more accurate (Cancer Causes Control 2008;19:437-42). After breast cancer, women are often followed with MRI with contrast and mammogram. Since both are problematic in pregnancy, 3-5 years may be more appropriate.

Many patients are concerned about the risk of recurrence during pregnancy. Though data are limited, pregnancy does not appear to increase the risk of disease recurrence or decrease disease-free survival, even in the case of more aggressive cancers such as melanoma. This remains true in the setting of hormone receptor–positive cancers, specifically breast cancer (Lancet 1997;350:319-22).

Preconception counseling

The risks for a cancer survivor during pregnancy will vary depending on the treatments she has received. Preconception evaluation should be modified for the specific oncologic therapies. For example, women who received chest radiation, or anthracycline-based chemotherapies (or any cardiotoxic medications) should have a cardiac evaluation as they are at risk of cardiac dysfunction prior to and during pregnancy (Matern. Child. Health J. 2006;10[suppl. 1]:165-8).

Additionally, because chemotherapy may be hepatotoxic or nephrotoxic, baseline liver and renal function tests should almost always be performed. It is not unreasonable to follow these during pregnancy given the physiologic changes.

Many women also are concerned about the risks that prior cancer therapies may have for their baby. Prior chemotherapy and radiation therapy do not appear to confer any increased risk for genetic conditions, anomalies, or childhood cancer (Am. J. Obstet. Gynecol. 2002;187:1070-80). Additionally, previous chemotherapy alone does not increase the risk of adverse pregnancy outcomes.

In contrast, prior radiation to the abdomen and pelvis has been associated with an increased risk of miscarriage, growth restriction, preterm delivery, and stillbirth (J. Natl. Cancer Instit. Monogr. 2005;34:64-8; Lancet 2010;376:624-30). There is an increased risk of cancer in the offspring of women whose cancer is the result of hereditary cancer syndromes, such as BRCA or hereditary nonpolyposis colorectal cancer. Discussions with a genetics counselor may be helpful if there are any questions related to these syndromes.

Pregnancy management

Once pregnant, management requires a multidisciplinary approach. Surveillance options are limited during pregnancy. CT should be avoided, and radiographs limited. Ultrasound of the abdomen is safe, but optimal images are often obscured in later trimesters. Ultimately, indicated imaging should not be forsaken if there are any signs or symptoms that raise concerns for recurrence. Additionally, many tumor markers may be unreliable during pregnancy, such as CA-125 in the first trimester, or alpha-FP and CEA anytime.

Specific recommendations for antenatal testing do not exist and should be assessed on a case-by-case basis; especially in the case of women who have had prior radiation therapy. Our recommendation is to perform growth surveillance, which may include sonography at varying intervals. Also consider weekly fetal testing from 32 weeks in normally growing fetuses.

Solely being a cancer survivor is not an indication for early delivery or induction of labor. In the majority of cases, mode of delivery should be guided by obstetric indications, though previous pelvic surgery and reconstruction may be indications for cesarean delivery. Despite being in remission, some cancers metastasize to the placenta, most commonly melanoma and hematologic cancers. Very rarely, these cancers can also metastasize to the fetus. Thus, the placenta should be sent for histologic evaluation, with a notation to the pathologist about the patient’s prior cancer (Obstet. Gynecol. Surv. 1989;44:535-40; Ultrasound. Obstet. Gynecol. 2009;33:235-44).

In most cases, pregnancy after cancer is uncomplicated with good outcomes for both mother and baby. However, there are potential medical and obstetric complications that cannot be overlooked. Interdisciplinary management is crucial to ensure a safe transition from cancer survivor to mother.

What to consider when counseling cancer survivors about pregnancy

• The recommended disease-free interval prior to pregnancy may vary by cancer type, and is largely driven by disease surveillance needs and recurrence intervals.

• Prior cancer, associated operations, and chemotherapies do not typically confer additional risks in pregnancy. Exceptions include melanoma and blood cell cancers, which may metastasize to the placenta and fetus, even following periods of remission.

• Radiation therapy to the abdomen and pelvis may induce changes that predispose to growth restriction, preterm birth, and stillbirth. Enhanced surveillance may be reasonable in these cases.

• Preconception or early pregnancy assessment for end organ dysfunction is recommended for women who have received certain therapies: cardiac evaluation following chest radiation or anthracycline-based therapy; liver and kidney function for most chemotherapies.

Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal and child health at the University of North Carolina at Chapel Hill. Dr. Dotters-Katz is a maternal-fetal medicine fellow at University of North Carolina at Chapel Hill, who completed her ob.gyn. residency at Duke University. Her academic interests include oncology and infectious diseases as they relate to pregnancy. The authors reported having no financial disclosures. Email them at [email protected].

Introduction

Stimulant medications are an important part of attention-deficit/hyperactivity disorder (ADHD) treatment for most affected children and teens. But studies suggest that children and teens may not take their prescribed medication anywhere from 13% to as much as 64% of the time. As teenagers develop an appropriate increased desire for autonomy, they wish to have greater participation in their medication decisions, sometimes to the dismay of their parents.

Case

Will is an engaging young man who has been on stimulants for many years. However, he is frequently in conflict with his parents over an array of issues, including being annoyed at being reminded to take his medications. Although he is willing to take medication some of the time, he often forgets. He commonly fails to complete his homework, a further source of conflict.

Discussion

Parents can get frustrated with their teens and drawn into a control struggle over medication and other issues. Teenagers want to have more control of their lives, and sometimes this takes the form of not wanting to take medication. The No. 1 goal is to help the family move away from digging themselves further into conflict, and instead to have a genuine discussion about the pros and cons of medication.

This starts with listening seriously to the teenager. It helps to reassure teens that you are not going to get mad at them for not taking medication, but that instead you really value the information about how often they are taking it and, if they are skipping some doses or not taking it at all, the reason for that.

It is crucial to find out the real reason why someone is not taking his medication. Sometimes teens are genuinely forgetting. Here it can be helpful to be sure that the medication has to be taken as few times a day as possible, and then to set some kind of alarm reminder. This is one area where the omnipresence of cell phones is very useful. Help parents and teens negotiate about whether the parent will remind the teen, as repeated reminders can be irritating. Divided pill containers help both the parent and teen know whether the medication has been taken or not. If you formulate a plan with the family, write it down so that you can ask next time how it worked out, because if you are asking someone to make a behavior change, it is important to pay attention to whether they did it or not.

Other times it is clear that the teen doesn’t want to take the medication. In this situation, it is important to get the specifics. It is key to convey that the teen’s point of view is very important.

Reasons for not wanting to take a medication include some type of side effect, embarrassment about having to take the medication in school, inconvenience, or a general feeling that the teen doesn’t want to be on medication.

A genuinely collaborative attitude is the best approach. Restate what you have heard from the teen about his or her viewpoint. Help the parents state their concerns (for instance, about school success, driving safety, or the potential for impulsive behavior) in a noncritical manner. Then outline options and discuss the possible pros and cons of the different choices, including going off the medication as one option. By considering this as an option, you will have an opportunity to discuss what the drawbacks, as well as the advantages, might be.

When it comes to ADHD, there are many choices. These can include trying a different stimulant or using a nonstimulant such as atomoxetine or an alpha-adrenergic agonist. Because these medications have very different side effect profiles, they may be more acceptable to the teenager, although they also may have different efficacy. There are also psychotherapeutic options such as organizational skills training. By discussing a variety of choices and listening to the teen’s concerns and hopes, the teenager is engaged in taking responsibility for his own choices.

Once a choice is decided upon, it is important to follow up and review how well the plan is working and revise if necessary.

When to consult

If parents and teens are unable to participate in discussion and come up with a plan, family therapy to improve communication and address parenting issues can be recommended.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said that she had no relevant financial disclosures. To comment, e-mail her at [email protected].

Introduction

Stimulant medications are an important part of attention-deficit/hyperactivity disorder (ADHD) treatment for most affected children and teens. But studies suggest that children and teens may not take their prescribed medication anywhere from 13% to as much as 64% of the time. As teenagers develop an appropriate increased desire for autonomy, they wish to have greater participation in their medication decisions, sometimes to the dismay of their parents.

Case

Will is an engaging young man who has been on stimulants for many years. However, he is frequently in conflict with his parents over an array of issues, including being annoyed at being reminded to take his medications. Although he is willing to take medication some of the time, he often forgets. He commonly fails to complete his homework, a further source of conflict.

Discussion

Parents can get frustrated with their teens and drawn into a control struggle over medication and other issues. Teenagers want to have more control of their lives, and sometimes this takes the form of not wanting to take medication. The No. 1 goal is to help the family move away from digging themselves further into conflict, and instead to have a genuine discussion about the pros and cons of medication.

This starts with listening seriously to the teenager. It helps to reassure teens that you are not going to get mad at them for not taking medication, but that instead you really value the information about how often they are taking it and, if they are skipping some doses or not taking it at all, the reason for that.

It is crucial to find out the real reason why someone is not taking his medication. Sometimes teens are genuinely forgetting. Here it can be helpful to be sure that the medication has to be taken as few times a day as possible, and then to set some kind of alarm reminder. This is one area where the omnipresence of cell phones is very useful. Help parents and teens negotiate about whether the parent will remind the teen, as repeated reminders can be irritating. Divided pill containers help both the parent and teen know whether the medication has been taken or not. If you formulate a plan with the family, write it down so that you can ask next time how it worked out, because if you are asking someone to make a behavior change, it is important to pay attention to whether they did it or not.

Other times it is clear that the teen doesn’t want to take the medication. In this situation, it is important to get the specifics. It is key to convey that the teen’s point of view is very important.

Reasons for not wanting to take a medication include some type of side effect, embarrassment about having to take the medication in school, inconvenience, or a general feeling that the teen doesn’t want to be on medication.

A genuinely collaborative attitude is the best approach. Restate what you have heard from the teen about his or her viewpoint. Help the parents state their concerns (for instance, about school success, driving safety, or the potential for impulsive behavior) in a noncritical manner. Then outline options and discuss the possible pros and cons of the different choices, including going off the medication as one option. By considering this as an option, you will have an opportunity to discuss what the drawbacks, as well as the advantages, might be.

When it comes to ADHD, there are many choices. These can include trying a different stimulant or using a nonstimulant such as atomoxetine or an alpha-adrenergic agonist. Because these medications have very different side effect profiles, they may be more acceptable to the teenager, although they also may have different efficacy. There are also psychotherapeutic options such as organizational skills training. By discussing a variety of choices and listening to the teen’s concerns and hopes, the teenager is engaged in taking responsibility for his own choices.

Once a choice is decided upon, it is important to follow up and review how well the plan is working and revise if necessary.

When to consult

If parents and teens are unable to participate in discussion and come up with a plan, family therapy to improve communication and address parenting issues can be recommended.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said that she had no relevant financial disclosures. To comment, e-mail her at [email protected].

Introduction

Stimulant medications are an important part of attention-deficit/hyperactivity disorder (ADHD) treatment for most affected children and teens. But studies suggest that children and teens may not take their prescribed medication anywhere from 13% to as much as 64% of the time. As teenagers develop an appropriate increased desire for autonomy, they wish to have greater participation in their medication decisions, sometimes to the dismay of their parents.

Case

Will is an engaging young man who has been on stimulants for many years. However, he is frequently in conflict with his parents over an array of issues, including being annoyed at being reminded to take his medications. Although he is willing to take medication some of the time, he often forgets. He commonly fails to complete his homework, a further source of conflict.

Discussion

Parents can get frustrated with their teens and drawn into a control struggle over medication and other issues. Teenagers want to have more control of their lives, and sometimes this takes the form of not wanting to take medication. The No. 1 goal is to help the family move away from digging themselves further into conflict, and instead to have a genuine discussion about the pros and cons of medication.

This starts with listening seriously to the teenager. It helps to reassure teens that you are not going to get mad at them for not taking medication, but that instead you really value the information about how often they are taking it and, if they are skipping some doses or not taking it at all, the reason for that.

It is crucial to find out the real reason why someone is not taking his medication. Sometimes teens are genuinely forgetting. Here it can be helpful to be sure that the medication has to be taken as few times a day as possible, and then to set some kind of alarm reminder. This is one area where the omnipresence of cell phones is very useful. Help parents and teens negotiate about whether the parent will remind the teen, as repeated reminders can be irritating. Divided pill containers help both the parent and teen know whether the medication has been taken or not. If you formulate a plan with the family, write it down so that you can ask next time how it worked out, because if you are asking someone to make a behavior change, it is important to pay attention to whether they did it or not.

Other times it is clear that the teen doesn’t want to take the medication. In this situation, it is important to get the specifics. It is key to convey that the teen’s point of view is very important.

Reasons for not wanting to take a medication include some type of side effect, embarrassment about having to take the medication in school, inconvenience, or a general feeling that the teen doesn’t want to be on medication.

A genuinely collaborative attitude is the best approach. Restate what you have heard from the teen about his or her viewpoint. Help the parents state their concerns (for instance, about school success, driving safety, or the potential for impulsive behavior) in a noncritical manner. Then outline options and discuss the possible pros and cons of the different choices, including going off the medication as one option. By considering this as an option, you will have an opportunity to discuss what the drawbacks, as well as the advantages, might be.

When it comes to ADHD, there are many choices. These can include trying a different stimulant or using a nonstimulant such as atomoxetine or an alpha-adrenergic agonist. Because these medications have very different side effect profiles, they may be more acceptable to the teenager, although they also may have different efficacy. There are also psychotherapeutic options such as organizational skills training. By discussing a variety of choices and listening to the teen’s concerns and hopes, the teenager is engaged in taking responsibility for his own choices.

Once a choice is decided upon, it is important to follow up and review how well the plan is working and revise if necessary.

When to consult

If parents and teens are unable to participate in discussion and come up with a plan, family therapy to improve communication and address parenting issues can be recommended.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said that she had no relevant financial disclosures. To comment, e-mail her at [email protected].