AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

Editors’ Note: This is the first installment of Curbside Consult, written by two Group for the Advancement of Psychiatry (GAP) committees – the Committee on Family Psychiatry and the Committee on Cultural Psychiatry.

Come back home

The patient is an unmarried Japanese man in his early 40s who presents with symptoms of social phobia. He was born and raised in Japan, and migrated to the United States to pursue a PhD. In Japan, he enjoyed middle-class status, but after immigrating to the United States, he has faced many financial difficulties. His language barriers have made him uncomfortable in front of his colleagues and supervisors and he has not been able to do well in his PhD program, ultimately leading to his expulsion. He does not want to go back to Japan, thinking he will not have a “good life” there. He believes that there is no respect for a person’s individuality in Japan. He is currently living in an urban location of New Jersey and works odd jobs. He states that his family does not understand his feelings about not returning to Japan, and instead they want him to support them. He has engaged in supportive psychotherapy and cognitive-behavioral therapy in the outpatient clinic along with psychopharmacological treatment.

Key questions

1. How is Japanese culture different from U.S. culture in terms of respecting a person’s individuality?

2. The expectations of the patient’s family are considered excessive by the patient. What is the role of Japanese culture in this situation?

3. In moving forward with treatment planning, what aspects of the patient’s culture should the clinician keep in mind?

Family perspective

This middle-aged Japanese man has had a challenging time since coming to the United States to study. He lives here alone. He has failed to achieve his goal of earning a PhD. He has had financial difficulties because of his job challenges. He has had the courage to seek mental health treatment, although the goals of his treatment are unclear. He is in contact with his family in Japan, who has asked that he come home, presumably to support his somewhat older parents. It is unclear who constitutes his “family.”

From a family perspective, it seems that the family/parents in Japan are expecting that family obligation will draw the man home while the patient is defying that expectation by seeking and building individuality in the United States. A family-oriented therapist would consider the patient’s relationship with his family and help him consider how to make his decision on where to live. The therapist also would support the patient in maintaining a connection with his family. The therapist would help the patient avoid both passively capitulating to his family and defiantly cutting off from them. This would entail discussing the role of family in the United States and Japan. It would be important to empower the patient to explore his reasons for wanting to stay in the United States, what he means by “a good life,” and what he senses as his obligation to his family.

The history of this man’s life in Japan, including recollections of his childhood and an understanding of the job history of other members of his family, will help the therapist understand this man and his experience of his family. The telling of the family narrative, from his perspective, may help the patient understand his wishes and his fears. Exploring his relationships with his mother and his father will help the therapist and the patient understand some of the problems he has had in the United States.

Given his current life circumstances, work, and social stresses, lack of social support, and problems functioning, he also should be clinically assessed for depression and any other significant mental health problems. Additional questions to explore include: Does he define himself as a “failure,” and what would it be like going back to Japan? Are there concerns about “losing face”? If his parents want him to support them, do they know about his financial situation? Would he be able to get a job in Japan, or would he end up living with his parents? Are their requests that he “come home” based on their need for support, or are they afraid that he really needs their help given his difficulties establishing a life here? As the patient explores these issues in more detail, he can begin the process of resolving his future.

Cultural psychiatry perspective

This case raises important cultural questions, which deserve further exploration in psychotherapy. Alternate approaches to evaluating culture in clinical settings have moved away from conceptualizing “U.S.” or “Japanese” cultures monolithically to understand how cultural dynamics matter to the individual.

Notably, clarifying what the patient means by the “individuality” that is “not respected in Japan” would be essential, as well as what he perceives as “excessive” in his family’s demands. Alan Roland, Ph.D., in his book “In Search of Self in India and Japan: Toward a Cross-Cultural Psychology” describes marked differences between traditional Japanese and U.S. expectations of family obligation and relationship: “dependence and interdependence with close emotional connectedness versus independence and autonomy; receptivity and deference to superiors in hierarchical relationships versus self-assertion and self-promotion in egalitarian-contractual relationships; communication on multiple levels and by innuendo versus verbal articulateness and forthrightness; maintaining and enhancing esteem at all costs versus forthright criticism and expressing the truth of the matter” (pp. 292-3).

Of course, these are intentionally polarized descriptions; yet many Japanese in the United States find themselves negotiating contrasting expectations about what it means to be a person in a family and a society, some finding value in at least parts of each tradition, some holding on to traditional Japanese values, and some adopting values related to the new environment.

A key question in this case is what made the situation so difficult for this patient. Going forward, the clinician will want to characterize the biopsychosocial etiologies of his symptoms. Are the social phobia symptoms related to premorbid developmental issues hindering communication, planning, and sociability? Were they exacerbated by language difficulties and the acculturation challenges of finding himself in a new country and institution with potentially different expectations of fulfillment and success?

One wonders how he was accepted into this PhD program and why his performance led to expulsion so quickly. Are there additional symptoms and impairments beyond the breakdown in communication? For example, are there depressive symptoms? Does he have other somatic symptomatology as part of his idiom of distress that may be magnifying his impairment? Were academic supports in place that could have prevented his expulsion? Does he have other social supports and relationships? Is he struggling with intense isolation and, potentially, individuation issues triggered by his new setting?

The DSM-5 Cultural Formulation Interview (CFI), a standardized method for conducting a cultural assessment in mental health care, could help the clinician elicit the patient’s understandings of the problem, its causes and contextual stressors and supports, cultural identity, the cultural features of the relationship between the patient and the clinician, and options for self-coping and clinical care. This exploration of the patient’s lifeworld may clarify how to intervene. Selected supplementary modules to the CFI also may also be useful to ‘amplify’ the core CFI and to further explore the patient’s perception of the family’s role in his illness, including the Social Network Module and the Psychosocial Stressors Module.

Contributors

John Sargent, M.D. – Tufts University School of Medicine

Ellen Berman, M.D. – University of Pennsylvania, Perelman School of Medicine

Roberto Lewis-Fernández, M.D. – Columbia University and New York State Psychiatric Institute

Robert C. Like, M.D., M.S. – Rutgers University, Robert Wood Johnson Medical School

Resources

Lewis-Fernández R., Aggarwal N.K., Baarnhielm, S., et al. Culture and Psychiatric Evaluation: Operationalizing Cultural Formulation for DSM-5 (Psychiatry 2014;77:130-54).

Roland A. In Search of Self in India and Japan: Toward a Cross-Cultural Psychology (Princeton,

N.J.: Princeton University Press, 1988).

Shibusawa T. Japanese Families, in Ethnicity and Family Therapy, 3rd edition. Edited by McGoldrick M., Giordano J., and Garcia-Preto. (New York: Guilford Press, 2005, pp. 339-48).

Tseng W.S., Chang S.C., Nishizono M., eds. Asian Culture and Psychotherapy: Implications for East and West (Honolulu: University of Hawai’i Press).

To read about the goals of Curbside Consult, the guiding principles for assessment, and the guidelines for case submission, see “Considering patients’ family, culture,” Clinical Psychiatry News, January 2015, p. 12. To contribute a case, send it to [email protected]. The contributors have revised selected patient details to shield the identities of the patients/cases and to comply with HIPAA requirements. This column is meant to be educational and does not constitute medical advice. The opinions expressed are those of the contributors and do not represent those of the organizations they employed by or affiliated with or the Group for the Advancement of Psychiatry (GAP).

Editors’ Note: This is the first installment of Curbside Consult, written by two Group for the Advancement of Psychiatry (GAP) committees – the Committee on Family Psychiatry and the Committee on Cultural Psychiatry.

Come back home

The patient is an unmarried Japanese man in his early 40s who presents with symptoms of social phobia. He was born and raised in Japan, and migrated to the United States to pursue a PhD. In Japan, he enjoyed middle-class status, but after immigrating to the United States, he has faced many financial difficulties. His language barriers have made him uncomfortable in front of his colleagues and supervisors and he has not been able to do well in his PhD program, ultimately leading to his expulsion. He does not want to go back to Japan, thinking he will not have a “good life” there. He believes that there is no respect for a person’s individuality in Japan. He is currently living in an urban location of New Jersey and works odd jobs. He states that his family does not understand his feelings about not returning to Japan, and instead they want him to support them. He has engaged in supportive psychotherapy and cognitive-behavioral therapy in the outpatient clinic along with psychopharmacological treatment.

Key questions

1. How is Japanese culture different from U.S. culture in terms of respecting a person’s individuality?

2. The expectations of the patient’s family are considered excessive by the patient. What is the role of Japanese culture in this situation?

3. In moving forward with treatment planning, what aspects of the patient’s culture should the clinician keep in mind?

Family perspective

This middle-aged Japanese man has had a challenging time since coming to the United States to study. He lives here alone. He has failed to achieve his goal of earning a PhD. He has had financial difficulties because of his job challenges. He has had the courage to seek mental health treatment, although the goals of his treatment are unclear. He is in contact with his family in Japan, who has asked that he come home, presumably to support his somewhat older parents. It is unclear who constitutes his “family.”

From a family perspective, it seems that the family/parents in Japan are expecting that family obligation will draw the man home while the patient is defying that expectation by seeking and building individuality in the United States. A family-oriented therapist would consider the patient’s relationship with his family and help him consider how to make his decision on where to live. The therapist also would support the patient in maintaining a connection with his family. The therapist would help the patient avoid both passively capitulating to his family and defiantly cutting off from them. This would entail discussing the role of family in the United States and Japan. It would be important to empower the patient to explore his reasons for wanting to stay in the United States, what he means by “a good life,” and what he senses as his obligation to his family.

The history of this man’s life in Japan, including recollections of his childhood and an understanding of the job history of other members of his family, will help the therapist understand this man and his experience of his family. The telling of the family narrative, from his perspective, may help the patient understand his wishes and his fears. Exploring his relationships with his mother and his father will help the therapist and the patient understand some of the problems he has had in the United States.

Given his current life circumstances, work, and social stresses, lack of social support, and problems functioning, he also should be clinically assessed for depression and any other significant mental health problems. Additional questions to explore include: Does he define himself as a “failure,” and what would it be like going back to Japan? Are there concerns about “losing face”? If his parents want him to support them, do they know about his financial situation? Would he be able to get a job in Japan, or would he end up living with his parents? Are their requests that he “come home” based on their need for support, or are they afraid that he really needs their help given his difficulties establishing a life here? As the patient explores these issues in more detail, he can begin the process of resolving his future.

Cultural psychiatry perspective

This case raises important cultural questions, which deserve further exploration in psychotherapy. Alternate approaches to evaluating culture in clinical settings have moved away from conceptualizing “U.S.” or “Japanese” cultures monolithically to understand how cultural dynamics matter to the individual.

Notably, clarifying what the patient means by the “individuality” that is “not respected in Japan” would be essential, as well as what he perceives as “excessive” in his family’s demands. Alan Roland, Ph.D., in his book “In Search of Self in India and Japan: Toward a Cross-Cultural Psychology” describes marked differences between traditional Japanese and U.S. expectations of family obligation and relationship: “dependence and interdependence with close emotional connectedness versus independence and autonomy; receptivity and deference to superiors in hierarchical relationships versus self-assertion and self-promotion in egalitarian-contractual relationships; communication on multiple levels and by innuendo versus verbal articulateness and forthrightness; maintaining and enhancing esteem at all costs versus forthright criticism and expressing the truth of the matter” (pp. 292-3).

Of course, these are intentionally polarized descriptions; yet many Japanese in the United States find themselves negotiating contrasting expectations about what it means to be a person in a family and a society, some finding value in at least parts of each tradition, some holding on to traditional Japanese values, and some adopting values related to the new environment.

A key question in this case is what made the situation so difficult for this patient. Going forward, the clinician will want to characterize the biopsychosocial etiologies of his symptoms. Are the social phobia symptoms related to premorbid developmental issues hindering communication, planning, and sociability? Were they exacerbated by language difficulties and the acculturation challenges of finding himself in a new country and institution with potentially different expectations of fulfillment and success?

One wonders how he was accepted into this PhD program and why his performance led to expulsion so quickly. Are there additional symptoms and impairments beyond the breakdown in communication? For example, are there depressive symptoms? Does he have other somatic symptomatology as part of his idiom of distress that may be magnifying his impairment? Were academic supports in place that could have prevented his expulsion? Does he have other social supports and relationships? Is he struggling with intense isolation and, potentially, individuation issues triggered by his new setting?

The DSM-5 Cultural Formulation Interview (CFI), a standardized method for conducting a cultural assessment in mental health care, could help the clinician elicit the patient’s understandings of the problem, its causes and contextual stressors and supports, cultural identity, the cultural features of the relationship between the patient and the clinician, and options for self-coping and clinical care. This exploration of the patient’s lifeworld may clarify how to intervene. Selected supplementary modules to the CFI also may also be useful to ‘amplify’ the core CFI and to further explore the patient’s perception of the family’s role in his illness, including the Social Network Module and the Psychosocial Stressors Module.

Contributors

John Sargent, M.D. – Tufts University School of Medicine

Ellen Berman, M.D. – University of Pennsylvania, Perelman School of Medicine

Roberto Lewis-Fernández, M.D. – Columbia University and New York State Psychiatric Institute

Robert C. Like, M.D., M.S. – Rutgers University, Robert Wood Johnson Medical School

Resources

Lewis-Fernández R., Aggarwal N.K., Baarnhielm, S., et al. Culture and Psychiatric Evaluation: Operationalizing Cultural Formulation for DSM-5 (Psychiatry 2014;77:130-54).

Roland A. In Search of Self in India and Japan: Toward a Cross-Cultural Psychology (Princeton,

N.J.: Princeton University Press, 1988).

Shibusawa T. Japanese Families, in Ethnicity and Family Therapy, 3rd edition. Edited by McGoldrick M., Giordano J., and Garcia-Preto. (New York: Guilford Press, 2005, pp. 339-48).

Tseng W.S., Chang S.C., Nishizono M., eds. Asian Culture and Psychotherapy: Implications for East and West (Honolulu: University of Hawai’i Press).

To read about the goals of Curbside Consult, the guiding principles for assessment, and the guidelines for case submission, see “Considering patients’ family, culture,” Clinical Psychiatry News, January 2015, p. 12. To contribute a case, send it to [email protected]. The contributors have revised selected patient details to shield the identities of the patients/cases and to comply with HIPAA requirements. This column is meant to be educational and does not constitute medical advice. The opinions expressed are those of the contributors and do not represent those of the organizations they employed by or affiliated with or the Group for the Advancement of Psychiatry (GAP).

Editors’ Note: This is the first installment of Curbside Consult, written by two Group for the Advancement of Psychiatry (GAP) committees – the Committee on Family Psychiatry and the Committee on Cultural Psychiatry.

Come back home

The patient is an unmarried Japanese man in his early 40s who presents with symptoms of social phobia. He was born and raised in Japan, and migrated to the United States to pursue a PhD. In Japan, he enjoyed middle-class status, but after immigrating to the United States, he has faced many financial difficulties. His language barriers have made him uncomfortable in front of his colleagues and supervisors and he has not been able to do well in his PhD program, ultimately leading to his expulsion. He does not want to go back to Japan, thinking he will not have a “good life” there. He believes that there is no respect for a person’s individuality in Japan. He is currently living in an urban location of New Jersey and works odd jobs. He states that his family does not understand his feelings about not returning to Japan, and instead they want him to support them. He has engaged in supportive psychotherapy and cognitive-behavioral therapy in the outpatient clinic along with psychopharmacological treatment.

Key questions

1. How is Japanese culture different from U.S. culture in terms of respecting a person’s individuality?

2. The expectations of the patient’s family are considered excessive by the patient. What is the role of Japanese culture in this situation?

3. In moving forward with treatment planning, what aspects of the patient’s culture should the clinician keep in mind?

Family perspective

This middle-aged Japanese man has had a challenging time since coming to the United States to study. He lives here alone. He has failed to achieve his goal of earning a PhD. He has had financial difficulties because of his job challenges. He has had the courage to seek mental health treatment, although the goals of his treatment are unclear. He is in contact with his family in Japan, who has asked that he come home, presumably to support his somewhat older parents. It is unclear who constitutes his “family.”

From a family perspective, it seems that the family/parents in Japan are expecting that family obligation will draw the man home while the patient is defying that expectation by seeking and building individuality in the United States. A family-oriented therapist would consider the patient’s relationship with his family and help him consider how to make his decision on where to live. The therapist also would support the patient in maintaining a connection with his family. The therapist would help the patient avoid both passively capitulating to his family and defiantly cutting off from them. This would entail discussing the role of family in the United States and Japan. It would be important to empower the patient to explore his reasons for wanting to stay in the United States, what he means by “a good life,” and what he senses as his obligation to his family.

The history of this man’s life in Japan, including recollections of his childhood and an understanding of the job history of other members of his family, will help the therapist understand this man and his experience of his family. The telling of the family narrative, from his perspective, may help the patient understand his wishes and his fears. Exploring his relationships with his mother and his father will help the therapist and the patient understand some of the problems he has had in the United States.

Given his current life circumstances, work, and social stresses, lack of social support, and problems functioning, he also should be clinically assessed for depression and any other significant mental health problems. Additional questions to explore include: Does he define himself as a “failure,” and what would it be like going back to Japan? Are there concerns about “losing face”? If his parents want him to support them, do they know about his financial situation? Would he be able to get a job in Japan, or would he end up living with his parents? Are their requests that he “come home” based on their need for support, or are they afraid that he really needs their help given his difficulties establishing a life here? As the patient explores these issues in more detail, he can begin the process of resolving his future.

Cultural psychiatry perspective

This case raises important cultural questions, which deserve further exploration in psychotherapy. Alternate approaches to evaluating culture in clinical settings have moved away from conceptualizing “U.S.” or “Japanese” cultures monolithically to understand how cultural dynamics matter to the individual.

Notably, clarifying what the patient means by the “individuality” that is “not respected in Japan” would be essential, as well as what he perceives as “excessive” in his family’s demands. Alan Roland, Ph.D., in his book “In Search of Self in India and Japan: Toward a Cross-Cultural Psychology” describes marked differences between traditional Japanese and U.S. expectations of family obligation and relationship: “dependence and interdependence with close emotional connectedness versus independence and autonomy; receptivity and deference to superiors in hierarchical relationships versus self-assertion and self-promotion in egalitarian-contractual relationships; communication on multiple levels and by innuendo versus verbal articulateness and forthrightness; maintaining and enhancing esteem at all costs versus forthright criticism and expressing the truth of the matter” (pp. 292-3).

Of course, these are intentionally polarized descriptions; yet many Japanese in the United States find themselves negotiating contrasting expectations about what it means to be a person in a family and a society, some finding value in at least parts of each tradition, some holding on to traditional Japanese values, and some adopting values related to the new environment.

A key question in this case is what made the situation so difficult for this patient. Going forward, the clinician will want to characterize the biopsychosocial etiologies of his symptoms. Are the social phobia symptoms related to premorbid developmental issues hindering communication, planning, and sociability? Were they exacerbated by language difficulties and the acculturation challenges of finding himself in a new country and institution with potentially different expectations of fulfillment and success?

One wonders how he was accepted into this PhD program and why his performance led to expulsion so quickly. Are there additional symptoms and impairments beyond the breakdown in communication? For example, are there depressive symptoms? Does he have other somatic symptomatology as part of his idiom of distress that may be magnifying his impairment? Were academic supports in place that could have prevented his expulsion? Does he have other social supports and relationships? Is he struggling with intense isolation and, potentially, individuation issues triggered by his new setting?

The DSM-5 Cultural Formulation Interview (CFI), a standardized method for conducting a cultural assessment in mental health care, could help the clinician elicit the patient’s understandings of the problem, its causes and contextual stressors and supports, cultural identity, the cultural features of the relationship between the patient and the clinician, and options for self-coping and clinical care. This exploration of the patient’s lifeworld may clarify how to intervene. Selected supplementary modules to the CFI also may also be useful to ‘amplify’ the core CFI and to further explore the patient’s perception of the family’s role in his illness, including the Social Network Module and the Psychosocial Stressors Module.

Contributors

John Sargent, M.D. – Tufts University School of Medicine

Ellen Berman, M.D. – University of Pennsylvania, Perelman School of Medicine

Roberto Lewis-Fernández, M.D. – Columbia University and New York State Psychiatric Institute

Robert C. Like, M.D., M.S. – Rutgers University, Robert Wood Johnson Medical School

Resources

Lewis-Fernández R., Aggarwal N.K., Baarnhielm, S., et al. Culture and Psychiatric Evaluation: Operationalizing Cultural Formulation for DSM-5 (Psychiatry 2014;77:130-54).

Roland A. In Search of Self in India and Japan: Toward a Cross-Cultural Psychology (Princeton,

N.J.: Princeton University Press, 1988).

Shibusawa T. Japanese Families, in Ethnicity and Family Therapy, 3rd edition. Edited by McGoldrick M., Giordano J., and Garcia-Preto. (New York: Guilford Press, 2005, pp. 339-48).

Tseng W.S., Chang S.C., Nishizono M., eds. Asian Culture and Psychotherapy: Implications for East and West (Honolulu: University of Hawai’i Press).

To read about the goals of Curbside Consult, the guiding principles for assessment, and the guidelines for case submission, see “Considering patients’ family, culture,” Clinical Psychiatry News, January 2015, p. 12. To contribute a case, send it to [email protected]. The contributors have revised selected patient details to shield the identities of the patients/cases and to comply with HIPAA requirements. This column is meant to be educational and does not constitute medical advice. The opinions expressed are those of the contributors and do not represent those of the organizations they employed by or affiliated with or the Group for the Advancement of Psychiatry (GAP).

Graduation season is rapidly approaching, with high school graduations, followed by summer vacations. While searching for that unique gift and /or summer experience, many of your patients may choose an international destination. Not to be forgotten are those who might travel to resource-limited areas to visit relatives, volunteer, or have extended stays because of parental job relocation. More U.S. high school graduates are participating in gap year programs, many of which involve extensive travel while providing the participant the opportunity to immerse and to actively participate in other cultures. For many, it may be their first experience in a country with poor hygiene. This week alone, I’ve helped prepare travelers, including adolescents and children, for a safari and one for 4 weeks of volunteerism in Tanzania. Another young traveler’s destinations were Rwanda, Uganda, and Kenya, and a fourth is planning to explore and trek regions in the high elevations of Bolivia and Peru. The question is, Will you be ready to help prepare young travelers to stay healthy and return home without any unwanted souvenirs?

For many, health concerns often are not the top priority when they are planning vacations. However, the primary care physician will most likely will be their initial call and resource once they realize their potential to be exposed to diseases and/or conditions not routinely encountered in the United States. Even if you receive the call late, there are still interventions you can provide.

To avoid that last-minute call, develop strategies to identify international travelers in your practice. Many practices send out reminders yearly for influenza and well visits, so consider developing one for international travel. Text-message reminders have been shown to improve influenza vaccine administration rates and are another form of communication that can be considered. Frequently remind families that if planning international travel, they should seek pretravel advice in a timely manner: Ideally advice should be obtained 4-6 weeks in advance, and definitely at least 2 weeks prior to departure. Remind them that adequate time is needed for the vaccine to become effective. In addition, depending on the patients’ destination, trip duration, and type of activity, two vaccines (rabies and Japanese encephalitis) may be recommended and are administered over a 28-day period. Yellow fever vaccine, which is recommended or required for entry into some countries, can be obtained only at centers designated by each state health department. It should be administered at least 10 days prior to travel.

Vaccine interventions are based on the potential risk for disease exposure/acquisition. Factors to consider include the age of the travelers, their health and immunization status, in addition to their destination, duration of stay, accommodations, activities, and reason for travel (such as business or visiting friends and relatives). If you have a child with a chronic disorder or who is immunocompromised, comparable medical care may not be available at all international destinations. In addition, not everyone may be a candidate to receive some recommended or required vaccines. Involvement with a health professional prior to booking the trip would be advisable.

Identify a travel health specialist in your area as a local resource who can provide the most up-to-date information and recommendations. Ensure that individual is willing to see children of all ages.

Make sure routine immunizations are up to date for age. Measles is the one exception. I know you have heard it before, but outbreaks persist, even in the United States. Travelers 6- to 11-months-old should receive one MMR dose prior to international travel. This dose will not count, so these children should receive two additional doses of vaccine once they are at least 1 year old. Many children travel with adults. All travelers at least 12 months of age and born after 1956 should have two documented doses of MMR prior to international travel unless they have serologic evidence of immunity. The second dose can be given as early as 4 weeks after the first. If two doses at least 4 weeks apart are administered when a child is at least 12 months of age, no additional doses are necessary.

In 2014, there were 668 cases of measles from 27 states in the United States. The United States is still experiencing a multistate outbreak of measles at press time, which began December 2014. As of April 24, 2015, 166 cases have been reported from 19 states. The Centers for Disease Control and Prevention analyzed the virus type (B3). It is identical to the one responsible for the outbreak in the Philippines in 2014, and it has now been identified in 14 other countries.

Most U.S. measles cases occur in unvaccinated travelers who become ill after their return and spread the disease to susceptible individuals. Do you have patients who are unimmunized? Another point to consider when speaking with these parents about travel is the potential loss of the herd immunity afforded their children while living in the United States. This benefit may not exist when they are visiting and/or relocating to countries with lower immunization rates. Measles outbreaks are occurring in multiple countries and are not limited to underdeveloped countries. For the most up-to-date travel health-related information from the CDC, click here.

Travelers’ diarrhea (TD) occurs in up to 70 % of travelers to developing countries. The World Health Organization defines it as passage of at least three loose stools in a 24-hour period. Most often it is self-limited, with symptoms lasting a median of 3-4 days. Although TD can be caused by bacteria, protozoa, and viruses, bacteria are usually the etiology, with enterotoxigenic Escherichia coli being the most common pathogens. Other bacterial etiologies include Shigella and Campylobacter species. Two antimicrobials are frequently prescribed to travelers for self-treatment of TD: ciprofloxacin and azithromycin. Most young children are prescribed the latter; however, in older children, ciprofloxacin may be prescribed off label, as its use in persons younger than 18 years is not approved by the Food and Drug Administration.

In December 2014, PulseNet, the national molecular subtyping network for food-borne disease, detected a multistate cluster of ciprofloxacin-resistant Shigella sonnei. Between May 2014 and February 2015, 157 cases including 37 children were detected in 32 states and Puerto Rico. Nine of the cases identified by PulseNet, and an additional 76 cases, were associated with an outbreak of ciprofloxacin-resistant S. sonnei in San Francisco. Antibiotic susceptibility was available for 126 isolates, of which 109 (87%) were not ciprofloxacin susceptible. Travel history was available for 75 patients not associated with the San Francisco outbreak, and slightly more than half (40) were associated with international travel. The island of Hispaniola (Dominican Republic = 22 cases and Haiti = 4 cases) was the most common destination, followed by India (8 cases) and Morocco (3 cases). The remaining destinations were Asia and Europe (MMWR 2015;64:318-20) Travel history was available and positive for 23 of the 37 children (62%).

Why such a concern? International travelers are at risk of becoming colonized with drug-resistant bacteria and have the potential to spread them domestically. It has already begun. In 2012, the National Antimicrobial Resistance Monitoring System (NARMS) revealed that isolates of S. sonnei had the following resistance pattern: trimethoprim/sulfamethoxazole, 42%; ampicillin, 18%; and ciprofloxacin, 2.1%. During this outbreak, 19 of the 126 isolates were tested by NARMS with the following resistance patterns noted: trimethoprim/sulfamethoxazole, 84%; ampicillin, 5%; and ciprofloxacin, 32%.

More judicious use of antibiotics is necessary. As pediatricians, we are not immune to this issue. The challenge is when, if at all, antibiotics should be prescribed for TD, and under what conditions should patients be instructed to use them. I’m rethinking my own practice. TD is one of the most common illnesses travelers acquire and is easily treated, but at what cost? The one expression I keep hearing myself say is, First do no harm.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures.

Graduation season is rapidly approaching, with high school graduations, followed by summer vacations. While searching for that unique gift and /or summer experience, many of your patients may choose an international destination. Not to be forgotten are those who might travel to resource-limited areas to visit relatives, volunteer, or have extended stays because of parental job relocation. More U.S. high school graduates are participating in gap year programs, many of which involve extensive travel while providing the participant the opportunity to immerse and to actively participate in other cultures. For many, it may be their first experience in a country with poor hygiene. This week alone, I’ve helped prepare travelers, including adolescents and children, for a safari and one for 4 weeks of volunteerism in Tanzania. Another young traveler’s destinations were Rwanda, Uganda, and Kenya, and a fourth is planning to explore and trek regions in the high elevations of Bolivia and Peru. The question is, Will you be ready to help prepare young travelers to stay healthy and return home without any unwanted souvenirs?

For many, health concerns often are not the top priority when they are planning vacations. However, the primary care physician will most likely will be their initial call and resource once they realize their potential to be exposed to diseases and/or conditions not routinely encountered in the United States. Even if you receive the call late, there are still interventions you can provide.

To avoid that last-minute call, develop strategies to identify international travelers in your practice. Many practices send out reminders yearly for influenza and well visits, so consider developing one for international travel. Text-message reminders have been shown to improve influenza vaccine administration rates and are another form of communication that can be considered. Frequently remind families that if planning international travel, they should seek pretravel advice in a timely manner: Ideally advice should be obtained 4-6 weeks in advance, and definitely at least 2 weeks prior to departure. Remind them that adequate time is needed for the vaccine to become effective. In addition, depending on the patients’ destination, trip duration, and type of activity, two vaccines (rabies and Japanese encephalitis) may be recommended and are administered over a 28-day period. Yellow fever vaccine, which is recommended or required for entry into some countries, can be obtained only at centers designated by each state health department. It should be administered at least 10 days prior to travel.

Vaccine interventions are based on the potential risk for disease exposure/acquisition. Factors to consider include the age of the travelers, their health and immunization status, in addition to their destination, duration of stay, accommodations, activities, and reason for travel (such as business or visiting friends and relatives). If you have a child with a chronic disorder or who is immunocompromised, comparable medical care may not be available at all international destinations. In addition, not everyone may be a candidate to receive some recommended or required vaccines. Involvement with a health professional prior to booking the trip would be advisable.

Identify a travel health specialist in your area as a local resource who can provide the most up-to-date information and recommendations. Ensure that individual is willing to see children of all ages.

Make sure routine immunizations are up to date for age. Measles is the one exception. I know you have heard it before, but outbreaks persist, even in the United States. Travelers 6- to 11-months-old should receive one MMR dose prior to international travel. This dose will not count, so these children should receive two additional doses of vaccine once they are at least 1 year old. Many children travel with adults. All travelers at least 12 months of age and born after 1956 should have two documented doses of MMR prior to international travel unless they have serologic evidence of immunity. The second dose can be given as early as 4 weeks after the first. If two doses at least 4 weeks apart are administered when a child is at least 12 months of age, no additional doses are necessary.

In 2014, there were 668 cases of measles from 27 states in the United States. The United States is still experiencing a multistate outbreak of measles at press time, which began December 2014. As of April 24, 2015, 166 cases have been reported from 19 states. The Centers for Disease Control and Prevention analyzed the virus type (B3). It is identical to the one responsible for the outbreak in the Philippines in 2014, and it has now been identified in 14 other countries.

Most U.S. measles cases occur in unvaccinated travelers who become ill after their return and spread the disease to susceptible individuals. Do you have patients who are unimmunized? Another point to consider when speaking with these parents about travel is the potential loss of the herd immunity afforded their children while living in the United States. This benefit may not exist when they are visiting and/or relocating to countries with lower immunization rates. Measles outbreaks are occurring in multiple countries and are not limited to underdeveloped countries. For the most up-to-date travel health-related information from the CDC, click here.

Travelers’ diarrhea (TD) occurs in up to 70 % of travelers to developing countries. The World Health Organization defines it as passage of at least three loose stools in a 24-hour period. Most often it is self-limited, with symptoms lasting a median of 3-4 days. Although TD can be caused by bacteria, protozoa, and viruses, bacteria are usually the etiology, with enterotoxigenic Escherichia coli being the most common pathogens. Other bacterial etiologies include Shigella and Campylobacter species. Two antimicrobials are frequently prescribed to travelers for self-treatment of TD: ciprofloxacin and azithromycin. Most young children are prescribed the latter; however, in older children, ciprofloxacin may be prescribed off label, as its use in persons younger than 18 years is not approved by the Food and Drug Administration.

In December 2014, PulseNet, the national molecular subtyping network for food-borne disease, detected a multistate cluster of ciprofloxacin-resistant Shigella sonnei. Between May 2014 and February 2015, 157 cases including 37 children were detected in 32 states and Puerto Rico. Nine of the cases identified by PulseNet, and an additional 76 cases, were associated with an outbreak of ciprofloxacin-resistant S. sonnei in San Francisco. Antibiotic susceptibility was available for 126 isolates, of which 109 (87%) were not ciprofloxacin susceptible. Travel history was available for 75 patients not associated with the San Francisco outbreak, and slightly more than half (40) were associated with international travel. The island of Hispaniola (Dominican Republic = 22 cases and Haiti = 4 cases) was the most common destination, followed by India (8 cases) and Morocco (3 cases). The remaining destinations were Asia and Europe (MMWR 2015;64:318-20) Travel history was available and positive for 23 of the 37 children (62%).

Why such a concern? International travelers are at risk of becoming colonized with drug-resistant bacteria and have the potential to spread them domestically. It has already begun. In 2012, the National Antimicrobial Resistance Monitoring System (NARMS) revealed that isolates of S. sonnei had the following resistance pattern: trimethoprim/sulfamethoxazole, 42%; ampicillin, 18%; and ciprofloxacin, 2.1%. During this outbreak, 19 of the 126 isolates were tested by NARMS with the following resistance patterns noted: trimethoprim/sulfamethoxazole, 84%; ampicillin, 5%; and ciprofloxacin, 32%.

More judicious use of antibiotics is necessary. As pediatricians, we are not immune to this issue. The challenge is when, if at all, antibiotics should be prescribed for TD, and under what conditions should patients be instructed to use them. I’m rethinking my own practice. TD is one of the most common illnesses travelers acquire and is easily treated, but at what cost? The one expression I keep hearing myself say is, First do no harm.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures.

Graduation season is rapidly approaching, with high school graduations, followed by summer vacations. While searching for that unique gift and /or summer experience, many of your patients may choose an international destination. Not to be forgotten are those who might travel to resource-limited areas to visit relatives, volunteer, or have extended stays because of parental job relocation. More U.S. high school graduates are participating in gap year programs, many of which involve extensive travel while providing the participant the opportunity to immerse and to actively participate in other cultures. For many, it may be their first experience in a country with poor hygiene. This week alone, I’ve helped prepare travelers, including adolescents and children, for a safari and one for 4 weeks of volunteerism in Tanzania. Another young traveler’s destinations were Rwanda, Uganda, and Kenya, and a fourth is planning to explore and trek regions in the high elevations of Bolivia and Peru. The question is, Will you be ready to help prepare young travelers to stay healthy and return home without any unwanted souvenirs?

For many, health concerns often are not the top priority when they are planning vacations. However, the primary care physician will most likely will be their initial call and resource once they realize their potential to be exposed to diseases and/or conditions not routinely encountered in the United States. Even if you receive the call late, there are still interventions you can provide.

To avoid that last-minute call, develop strategies to identify international travelers in your practice. Many practices send out reminders yearly for influenza and well visits, so consider developing one for international travel. Text-message reminders have been shown to improve influenza vaccine administration rates and are another form of communication that can be considered. Frequently remind families that if planning international travel, they should seek pretravel advice in a timely manner: Ideally advice should be obtained 4-6 weeks in advance, and definitely at least 2 weeks prior to departure. Remind them that adequate time is needed for the vaccine to become effective. In addition, depending on the patients’ destination, trip duration, and type of activity, two vaccines (rabies and Japanese encephalitis) may be recommended and are administered over a 28-day period. Yellow fever vaccine, which is recommended or required for entry into some countries, can be obtained only at centers designated by each state health department. It should be administered at least 10 days prior to travel.

Vaccine interventions are based on the potential risk for disease exposure/acquisition. Factors to consider include the age of the travelers, their health and immunization status, in addition to their destination, duration of stay, accommodations, activities, and reason for travel (such as business or visiting friends and relatives). If you have a child with a chronic disorder or who is immunocompromised, comparable medical care may not be available at all international destinations. In addition, not everyone may be a candidate to receive some recommended or required vaccines. Involvement with a health professional prior to booking the trip would be advisable.

Identify a travel health specialist in your area as a local resource who can provide the most up-to-date information and recommendations. Ensure that individual is willing to see children of all ages.

Make sure routine immunizations are up to date for age. Measles is the one exception. I know you have heard it before, but outbreaks persist, even in the United States. Travelers 6- to 11-months-old should receive one MMR dose prior to international travel. This dose will not count, so these children should receive two additional doses of vaccine once they are at least 1 year old. Many children travel with adults. All travelers at least 12 months of age and born after 1956 should have two documented doses of MMR prior to international travel unless they have serologic evidence of immunity. The second dose can be given as early as 4 weeks after the first. If two doses at least 4 weeks apart are administered when a child is at least 12 months of age, no additional doses are necessary.

In 2014, there were 668 cases of measles from 27 states in the United States. The United States is still experiencing a multistate outbreak of measles at press time, which began December 2014. As of April 24, 2015, 166 cases have been reported from 19 states. The Centers for Disease Control and Prevention analyzed the virus type (B3). It is identical to the one responsible for the outbreak in the Philippines in 2014, and it has now been identified in 14 other countries.

Most U.S. measles cases occur in unvaccinated travelers who become ill after their return and spread the disease to susceptible individuals. Do you have patients who are unimmunized? Another point to consider when speaking with these parents about travel is the potential loss of the herd immunity afforded their children while living in the United States. This benefit may not exist when they are visiting and/or relocating to countries with lower immunization rates. Measles outbreaks are occurring in multiple countries and are not limited to underdeveloped countries. For the most up-to-date travel health-related information from the CDC, click here.

Travelers’ diarrhea (TD) occurs in up to 70 % of travelers to developing countries. The World Health Organization defines it as passage of at least three loose stools in a 24-hour period. Most often it is self-limited, with symptoms lasting a median of 3-4 days. Although TD can be caused by bacteria, protozoa, and viruses, bacteria are usually the etiology, with enterotoxigenic Escherichia coli being the most common pathogens. Other bacterial etiologies include Shigella and Campylobacter species. Two antimicrobials are frequently prescribed to travelers for self-treatment of TD: ciprofloxacin and azithromycin. Most young children are prescribed the latter; however, in older children, ciprofloxacin may be prescribed off label, as its use in persons younger than 18 years is not approved by the Food and Drug Administration.

In December 2014, PulseNet, the national molecular subtyping network for food-borne disease, detected a multistate cluster of ciprofloxacin-resistant Shigella sonnei. Between May 2014 and February 2015, 157 cases including 37 children were detected in 32 states and Puerto Rico. Nine of the cases identified by PulseNet, and an additional 76 cases, were associated with an outbreak of ciprofloxacin-resistant S. sonnei in San Francisco. Antibiotic susceptibility was available for 126 isolates, of which 109 (87%) were not ciprofloxacin susceptible. Travel history was available for 75 patients not associated with the San Francisco outbreak, and slightly more than half (40) were associated with international travel. The island of Hispaniola (Dominican Republic = 22 cases and Haiti = 4 cases) was the most common destination, followed by India (8 cases) and Morocco (3 cases). The remaining destinations were Asia and Europe (MMWR 2015;64:318-20) Travel history was available and positive for 23 of the 37 children (62%).

Why such a concern? International travelers are at risk of becoming colonized with drug-resistant bacteria and have the potential to spread them domestically. It has already begun. In 2012, the National Antimicrobial Resistance Monitoring System (NARMS) revealed that isolates of S. sonnei had the following resistance pattern: trimethoprim/sulfamethoxazole, 42%; ampicillin, 18%; and ciprofloxacin, 2.1%. During this outbreak, 19 of the 126 isolates were tested by NARMS with the following resistance patterns noted: trimethoprim/sulfamethoxazole, 84%; ampicillin, 5%; and ciprofloxacin, 32%.

More judicious use of antibiotics is necessary. As pediatricians, we are not immune to this issue. The challenge is when, if at all, antibiotics should be prescribed for TD, and under what conditions should patients be instructed to use them. I’m rethinking my own practice. TD is one of the most common illnesses travelers acquire and is easily treated, but at what cost? The one expression I keep hearing myself say is, First do no harm.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures.

Disturbances in family emotional involvement are best understood at the extremes. At one end, there is extreme cutoff in the controversial diagnosis of parental alienation. At the other end is the extreme enmeshment in shared delusional disorders. What are the mechanisms that allow these conditions to develop? Helping families understand these mechanisms can help them change the trajectory of the family, by moving toward the middle, toward appropriate family emotional involvement.

How does enmeshment begin?

Good parents want to instill good morals, values, and behaviors in their children. Good parents want to teach their children to be good citizens, have good manners, and to treat others with respect. However, sometimes parents desire something more from their children; they want their children to continue a family business, be part of their religious organization, or to be “just like us.” Parental influence is easier when communities are isolated. When shared family beliefs are pervasive and impede the individuation of thoughts, feelings, and behaviors, these families are considered enmeshed and undifferentiated. Enmeshed families are more susceptible to indoctrination. Indoctrination is easier when there is a high level of emotional involvement, meaning that children are kept close, and differentiation and individuation are discouraged.

Using a child for one’s own needs is exploitative;however, many parents might not understand how their own unconscious psychological needs affect their children. This is seen clearly when children are rejected because they are “different.” For example, some parents have stated that a lesbian, gay, bisexual, and transgender sexual orientation is “against their religion,” and demand that their child conform to the family beliefs and norms. In these cases, the adolescent or young adult has to decide whether to leave the family, conform to its beliefs, or hide his or her identity.

Enmeshment

Emotional overinvolvement in undifferentiated enmeshed families is central to the diagnosis of shared delusional disorder. One example of a shared delusion is delusional parasitosis. This is a rare delusional disorder where the patient is convinced of being infested with worms, insects, parasites, or bacteria while no objective evidence exists to support this belief. Somatic delusions are shared with one or more members of a family in 5%-15% of cases (J. Behav. Health 2014;3:200-2).

Salvador Minuchin, Ph.D., and his colleagues outlined the impact of enmeshment in families where a child has an eating disorder. They described children so overprotected that there was a virtual moat around the family system, blocking out the world. Interpersonal differentiation in an enmeshed family system was poor, with identity fusion between parent and child. In this dynamic, the child is unable to establish a clear identity apart from the parent. Orthorexia, a term coined in 1997 by Dr. Steven Bratman, is defined as an obsession with “healthy or righteous eating.” The obsession with healthy foods can be structured within family habits. When enmeshment and family isolation are present, orthorexia can show up as a folie à famille (Heru, personal experience).

More exotic examples are known by the French terms folie à deux and folie à famille. Dr. Ernest-Charles Lasegue (Ann. Med. Psychol. 1877;18:321) was the first person to describe folie à deux. He stated that the inducer created the delusions from his/her psychosis and imposed them upon a “passive” individual; the induced subject was not truly psychotic but instead “absurdly credulous.” Several varieties are described. Folie imposée is the one we typically think of, where the naive individual has a resolution of symptoms when removed from the dominant person. Folie simultanée is where simultaneous and identical psychoses occur in two predisposed people who have had a long and intimate association with each other. There is usually no dominant partner, and separation does not alleviate the symptomatology. Folie communiquée involves the transfer of psychotic delusions after a long period of resistance by the passive partner. The recipient of the delusions subsequently develops his own delusions, independent of the primary subject’s, and these persist following separation.

Folie induite, a variant of folie communiquée, is diagnosed when new delusions are added to old ones under the influence of another deluded patient. The secondary person enriches the newly acquired delusions. Another method of classification is based on the number of individuals involved: folie à trois (three), folie à quatre (four), folie à cinq (five), and, as mentioned earlier, folie àfamille.

What is the mechanism for enmeshment? Several predisposing factors can occur: social isolation, the presence of a naive or “absurdly credulous” person, and in the case of relatives, a shared genetic predisposition. It is most common for the dominant person to drive the belief that is then accepted by dependent family members. In the case of children, there is also identification with a parent and a lack of drive for separation.

Role of alienation

At the opposite end of the spectrum is alienation, most publicly described in the disputed diagnosis of parental alienation syndrome (PAS) (The Parental Alienation Syndrome, 2nd ed., Cresskill, N.J.:Creative Therapeutics Inc., 1998). PAS sometimes arises in the context of child-custody disputes. The primary manifestation is the child’s unjustified denigration of one parent. According to Dr. William Bernet and Amy J.L. Baker, Ph.D., PAS features “abnormal, maladaptive behavior (refusal to have a relationship with a loving parent) that is driven by an abnormal mental state (the false belief that the rejected parent is evil, dangerous, or unworthy of love)” (J. Am. Acad. Psychiatry Law 2013;41:98-104). There is considered to be brainwashing of the child by one parent against the other parent in order to gain leverage in a court of law.

What is the mechanism in alienation? Enmeshment and overidentification of the child with the favored custodial parent is common. The child depends on this adult for his survival. The process of divorce can increase enmeshment with the custodial parent. The parent might reinforce the enmeshment by instilling fear of the “other” parent. The belief that the “other parent” is “bad” is transmitted through conscious and unconscious mechanisms.

The conscious mechanism is direct expression of anger toward the alienated parent. The anger might be motivated by rejection or as revenge for rejection with a desire to punish. The unconscious mechanisms include projective identification. In this situation, anger is seen as being embodied within the “other.” The projecting parent who continues to “hate” keeps the children tied to her out of projected fear of the “other.” The parent who uses projection is likely to have a primitive character structure. The child of the narcissistic custodial parent then acts out the shame and rage at the failure of the marriage.

These domestic tragedies have been around since the beginning of time. In Greek mythology, Medea, having been abandoned by Jason, took her revenge by murdering her two children. “Hell hath no fury like a woman scorned” is a paraphrase from William Congreve’s The Mourning Bride (1697).

What does the DSM-5 say?

Are these disorders and syndromes “real” psychiatric illnesses? The DSM-5 no longer separates delusional disorder from shared delusional disorder. If criteria are met for delusional disorder, that diagnosis is made. If the diagnosis cannot be made but shared beliefs are present, the diagnosis “other specified schizophrenia spectrum and other psychotic disorder” is used.

Those who advocated for inclusion of PAS cited the benefits that follow from a legitimate diagnosis such as legitimatizing problems that family therapists and psychotherapists encounter, allowing insurance coverage, and stimulating research. However, PAS was rejected as not having a good enough scientific basis.

Managing affective involvement

How does the psychiatrist manage families where emotional involvement is extreme? Psychiatrists first need to decide whether the family is capable of making changes and is willing to work on structural change within the family. If not, we can help patients remove themselves from destructive family situations. If the patient in your office wants to leave the family system or minimize the impact of the family system, individual psychotherapy that identifies the impact of family dysfunction, such as cognitive-behavioral therapy, can be used as a type of deprogramming. Exit strategies also can be discussed.

Al-Anon, for example, clarifies the influence of the family system on family members’ well-being by asking several questions, including:

Do you tell lies to cover up for someone else’s drinking?

Do you feel that if they cared about you, they would stop drinking to please you?

Do you make threats, such as, “If you don’t stop drinking, I’ll leave you?”

Are you afraid to upset someone for fear it will set off a drinking bout?

Have you considered calling the police for help in fear of abuse?

Do you feel like a failure because you can’t control the drinking?

Do you think that if they stopped drinking, your other problems would be solved?

If you think there is capacity for family change, the following strategies are helpful:

1. Education about appropriate differentiation

According to Dr. Murray Bowen, one of the main tasks of individuation is finding the right level of differentiation from parents. At one end of the differentiation spectrum is emotional fusion, and at the other end is emotional cutoff (disconnection between family members or refusal to engage with certain family members) (see “Family Evaluation,” New York: W.W. Norton & Co., 1988).

When family enmeshment is present, we can educate the family about individuation. In this way, the family develops a greater intellectual understanding of how they function, compared to their cultural norm. The family may benefit from creating a genogram that clarifies patterns of emotional involvement in their family of origin. Look for intergenerational patterns, and discuss how emotional differentiation occurred in prior generations. Teach the family about the emotional tasks of differentiation.

2. If there is alienation, parse out the reasons

Clarify conscious mechanisms that force the child to reject the other parent. Help the parent understand the consequences for the child in having no access to the other parent. Again, using a genogram helps identify intergenerational patterns, such as emotional cutoffs. Explore the reason for prior family emotional cutoffs. Identify typical patterns in the family for managing anger and conflicts.

In cases of divorce of the custodial parent, look at how anger is managed and stages of grief. Look for the presence of narcissistic injury. Discuss what a good divorce is and the healthiest way for the child to grow up. Help the parent manage and process her own affect without contaminating the child. It is not the role of the child to be the parental caregiver.

Help the child see that there was a loving relationship in the past and that new family goals can be created. The child also might experience anger and grief, and it is important to educate the child about how to manage those feelings appropriately rather than using blame and alienation. Help the child be empowered by positive ideals rather than negative emotions.

Psychiatrists often avoid working with these families, and perceive them as stuck and unable to change. This might be true for some families but certainly not all. Many families find themselves in situations that they do not understand and with problems they need help resolving. Educating and working with families who are stuck and who ask for and want change can change the life trajectory of many people.

Dr. Heru is with the department of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).

Disturbances in family emotional involvement are best understood at the extremes. At one end, there is extreme cutoff in the controversial diagnosis of parental alienation. At the other end is the extreme enmeshment in shared delusional disorders. What are the mechanisms that allow these conditions to develop? Helping families understand these mechanisms can help them change the trajectory of the family, by moving toward the middle, toward appropriate family emotional involvement.

How does enmeshment begin?

Good parents want to instill good morals, values, and behaviors in their children. Good parents want to teach their children to be good citizens, have good manners, and to treat others with respect. However, sometimes parents desire something more from their children; they want their children to continue a family business, be part of their religious organization, or to be “just like us.” Parental influence is easier when communities are isolated. When shared family beliefs are pervasive and impede the individuation of thoughts, feelings, and behaviors, these families are considered enmeshed and undifferentiated. Enmeshed families are more susceptible to indoctrination. Indoctrination is easier when there is a high level of emotional involvement, meaning that children are kept close, and differentiation and individuation are discouraged.

Using a child for one’s own needs is exploitative;however, many parents might not understand how their own unconscious psychological needs affect their children. This is seen clearly when children are rejected because they are “different.” For example, some parents have stated that a lesbian, gay, bisexual, and transgender sexual orientation is “against their religion,” and demand that their child conform to the family beliefs and norms. In these cases, the adolescent or young adult has to decide whether to leave the family, conform to its beliefs, or hide his or her identity.

Enmeshment

Emotional overinvolvement in undifferentiated enmeshed families is central to the diagnosis of shared delusional disorder. One example of a shared delusion is delusional parasitosis. This is a rare delusional disorder where the patient is convinced of being infested with worms, insects, parasites, or bacteria while no objective evidence exists to support this belief. Somatic delusions are shared with one or more members of a family in 5%-15% of cases (J. Behav. Health 2014;3:200-2).

Salvador Minuchin, Ph.D., and his colleagues outlined the impact of enmeshment in families where a child has an eating disorder. They described children so overprotected that there was a virtual moat around the family system, blocking out the world. Interpersonal differentiation in an enmeshed family system was poor, with identity fusion between parent and child. In this dynamic, the child is unable to establish a clear identity apart from the parent. Orthorexia, a term coined in 1997 by Dr. Steven Bratman, is defined as an obsession with “healthy or righteous eating.” The obsession with healthy foods can be structured within family habits. When enmeshment and family isolation are present, orthorexia can show up as a folie à famille (Heru, personal experience).

More exotic examples are known by the French terms folie à deux and folie à famille. Dr. Ernest-Charles Lasegue (Ann. Med. Psychol. 1877;18:321) was the first person to describe folie à deux. He stated that the inducer created the delusions from his/her psychosis and imposed them upon a “passive” individual; the induced subject was not truly psychotic but instead “absurdly credulous.” Several varieties are described. Folie imposée is the one we typically think of, where the naive individual has a resolution of symptoms when removed from the dominant person. Folie simultanée is where simultaneous and identical psychoses occur in two predisposed people who have had a long and intimate association with each other. There is usually no dominant partner, and separation does not alleviate the symptomatology. Folie communiquée involves the transfer of psychotic delusions after a long period of resistance by the passive partner. The recipient of the delusions subsequently develops his own delusions, independent of the primary subject’s, and these persist following separation.

Folie induite, a variant of folie communiquée, is diagnosed when new delusions are added to old ones under the influence of another deluded patient. The secondary person enriches the newly acquired delusions. Another method of classification is based on the number of individuals involved: folie à trois (three), folie à quatre (four), folie à cinq (five), and, as mentioned earlier, folie àfamille.

What is the mechanism for enmeshment? Several predisposing factors can occur: social isolation, the presence of a naive or “absurdly credulous” person, and in the case of relatives, a shared genetic predisposition. It is most common for the dominant person to drive the belief that is then accepted by dependent family members. In the case of children, there is also identification with a parent and a lack of drive for separation.

Role of alienation

At the opposite end of the spectrum is alienation, most publicly described in the disputed diagnosis of parental alienation syndrome (PAS) (The Parental Alienation Syndrome, 2nd ed., Cresskill, N.J.:Creative Therapeutics Inc., 1998). PAS sometimes arises in the context of child-custody disputes. The primary manifestation is the child’s unjustified denigration of one parent. According to Dr. William Bernet and Amy J.L. Baker, Ph.D., PAS features “abnormal, maladaptive behavior (refusal to have a relationship with a loving parent) that is driven by an abnormal mental state (the false belief that the rejected parent is evil, dangerous, or unworthy of love)” (J. Am. Acad. Psychiatry Law 2013;41:98-104). There is considered to be brainwashing of the child by one parent against the other parent in order to gain leverage in a court of law.

What is the mechanism in alienation? Enmeshment and overidentification of the child with the favored custodial parent is common. The child depends on this adult for his survival. The process of divorce can increase enmeshment with the custodial parent. The parent might reinforce the enmeshment by instilling fear of the “other” parent. The belief that the “other parent” is “bad” is transmitted through conscious and unconscious mechanisms.

The conscious mechanism is direct expression of anger toward the alienated parent. The anger might be motivated by rejection or as revenge for rejection with a desire to punish. The unconscious mechanisms include projective identification. In this situation, anger is seen as being embodied within the “other.” The projecting parent who continues to “hate” keeps the children tied to her out of projected fear of the “other.” The parent who uses projection is likely to have a primitive character structure. The child of the narcissistic custodial parent then acts out the shame and rage at the failure of the marriage.

These domestic tragedies have been around since the beginning of time. In Greek mythology, Medea, having been abandoned by Jason, took her revenge by murdering her two children. “Hell hath no fury like a woman scorned” is a paraphrase from William Congreve’s The Mourning Bride (1697).

What does the DSM-5 say?

Are these disorders and syndromes “real” psychiatric illnesses? The DSM-5 no longer separates delusional disorder from shared delusional disorder. If criteria are met for delusional disorder, that diagnosis is made. If the diagnosis cannot be made but shared beliefs are present, the diagnosis “other specified schizophrenia spectrum and other psychotic disorder” is used.

Those who advocated for inclusion of PAS cited the benefits that follow from a legitimate diagnosis such as legitimatizing problems that family therapists and psychotherapists encounter, allowing insurance coverage, and stimulating research. However, PAS was rejected as not having a good enough scientific basis.

Managing affective involvement

How does the psychiatrist manage families where emotional involvement is extreme? Psychiatrists first need to decide whether the family is capable of making changes and is willing to work on structural change within the family. If not, we can help patients remove themselves from destructive family situations. If the patient in your office wants to leave the family system or minimize the impact of the family system, individual psychotherapy that identifies the impact of family dysfunction, such as cognitive-behavioral therapy, can be used as a type of deprogramming. Exit strategies also can be discussed.

Al-Anon, for example, clarifies the influence of the family system on family members’ well-being by asking several questions, including:

Do you tell lies to cover up for someone else’s drinking?

Do you feel that if they cared about you, they would stop drinking to please you?

Do you make threats, such as, “If you don’t stop drinking, I’ll leave you?”

Are you afraid to upset someone for fear it will set off a drinking bout?

Have you considered calling the police for help in fear of abuse?

Do you feel like a failure because you can’t control the drinking?

Do you think that if they stopped drinking, your other problems would be solved?

If you think there is capacity for family change, the following strategies are helpful:

1. Education about appropriate differentiation

According to Dr. Murray Bowen, one of the main tasks of individuation is finding the right level of differentiation from parents. At one end of the differentiation spectrum is emotional fusion, and at the other end is emotional cutoff (disconnection between family members or refusal to engage with certain family members) (see “Family Evaluation,” New York: W.W. Norton & Co., 1988).

When family enmeshment is present, we can educate the family about individuation. In this way, the family develops a greater intellectual understanding of how they function, compared to their cultural norm. The family may benefit from creating a genogram that clarifies patterns of emotional involvement in their family of origin. Look for intergenerational patterns, and discuss how emotional differentiation occurred in prior generations. Teach the family about the emotional tasks of differentiation.

2. If there is alienation, parse out the reasons

Clarify conscious mechanisms that force the child to reject the other parent. Help the parent understand the consequences for the child in having no access to the other parent. Again, using a genogram helps identify intergenerational patterns, such as emotional cutoffs. Explore the reason for prior family emotional cutoffs. Identify typical patterns in the family for managing anger and conflicts.

In cases of divorce of the custodial parent, look at how anger is managed and stages of grief. Look for the presence of narcissistic injury. Discuss what a good divorce is and the healthiest way for the child to grow up. Help the parent manage and process her own affect without contaminating the child. It is not the role of the child to be the parental caregiver.

Help the child see that there was a loving relationship in the past and that new family goals can be created. The child also might experience anger and grief, and it is important to educate the child about how to manage those feelings appropriately rather than using blame and alienation. Help the child be empowered by positive ideals rather than negative emotions.

Psychiatrists often avoid working with these families, and perceive them as stuck and unable to change. This might be true for some families but certainly not all. Many families find themselves in situations that they do not understand and with problems they need help resolving. Educating and working with families who are stuck and who ask for and want change can change the life trajectory of many people.

Dr. Heru is with the department of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).

Disturbances in family emotional involvement are best understood at the extremes. At one end, there is extreme cutoff in the controversial diagnosis of parental alienation. At the other end is the extreme enmeshment in shared delusional disorders. What are the mechanisms that allow these conditions to develop? Helping families understand these mechanisms can help them change the trajectory of the family, by moving toward the middle, toward appropriate family emotional involvement.

How does enmeshment begin?

Good parents want to instill good morals, values, and behaviors in their children. Good parents want to teach their children to be good citizens, have good manners, and to treat others with respect. However, sometimes parents desire something more from their children; they want their children to continue a family business, be part of their religious organization, or to be “just like us.” Parental influence is easier when communities are isolated. When shared family beliefs are pervasive and impede the individuation of thoughts, feelings, and behaviors, these families are considered enmeshed and undifferentiated. Enmeshed families are more susceptible to indoctrination. Indoctrination is easier when there is a high level of emotional involvement, meaning that children are kept close, and differentiation and individuation are discouraged.

Using a child for one’s own needs is exploitative;however, many parents might not understand how their own unconscious psychological needs affect their children. This is seen clearly when children are rejected because they are “different.” For example, some parents have stated that a lesbian, gay, bisexual, and transgender sexual orientation is “against their religion,” and demand that their child conform to the family beliefs and norms. In these cases, the adolescent or young adult has to decide whether to leave the family, conform to its beliefs, or hide his or her identity.

Enmeshment

Emotional overinvolvement in undifferentiated enmeshed families is central to the diagnosis of shared delusional disorder. One example of a shared delusion is delusional parasitosis. This is a rare delusional disorder where the patient is convinced of being infested with worms, insects, parasites, or bacteria while no objective evidence exists to support this belief. Somatic delusions are shared with one or more members of a family in 5%-15% of cases (J. Behav. Health 2014;3:200-2).

Salvador Minuchin, Ph.D., and his colleagues outlined the impact of enmeshment in families where a child has an eating disorder. They described children so overprotected that there was a virtual moat around the family system, blocking out the world. Interpersonal differentiation in an enmeshed family system was poor, with identity fusion between parent and child. In this dynamic, the child is unable to establish a clear identity apart from the parent. Orthorexia, a term coined in 1997 by Dr. Steven Bratman, is defined as an obsession with “healthy or righteous eating.” The obsession with healthy foods can be structured within family habits. When enmeshment and family isolation are present, orthorexia can show up as a folie à famille (Heru, personal experience).

More exotic examples are known by the French terms folie à deux and folie à famille. Dr. Ernest-Charles Lasegue (Ann. Med. Psychol. 1877;18:321) was the first person to describe folie à deux. He stated that the inducer created the delusions from his/her psychosis and imposed them upon a “passive” individual; the induced subject was not truly psychotic but instead “absurdly credulous.” Several varieties are described. Folie imposée is the one we typically think of, where the naive individual has a resolution of symptoms when removed from the dominant person. Folie simultanée is where simultaneous and identical psychoses occur in two predisposed people who have had a long and intimate association with each other. There is usually no dominant partner, and separation does not alleviate the symptomatology. Folie communiquée involves the transfer of psychotic delusions after a long period of resistance by the passive partner. The recipient of the delusions subsequently develops his own delusions, independent of the primary subject’s, and these persist following separation.

Folie induite, a variant of folie communiquée, is diagnosed when new delusions are added to old ones under the influence of another deluded patient. The secondary person enriches the newly acquired delusions. Another method of classification is based on the number of individuals involved: folie à trois (three), folie à quatre (four), folie à cinq (five), and, as mentioned earlier, folie àfamille.

What is the mechanism for enmeshment? Several predisposing factors can occur: social isolation, the presence of a naive or “absurdly credulous” person, and in the case of relatives, a shared genetic predisposition. It is most common for the dominant person to drive the belief that is then accepted by dependent family members. In the case of children, there is also identification with a parent and a lack of drive for separation.

Role of alienation

At the opposite end of the spectrum is alienation, most publicly described in the disputed diagnosis of parental alienation syndrome (PAS) (The Parental Alienation Syndrome, 2nd ed., Cresskill, N.J.:Creative Therapeutics Inc., 1998). PAS sometimes arises in the context of child-custody disputes. The primary manifestation is the child’s unjustified denigration of one parent. According to Dr. William Bernet and Amy J.L. Baker, Ph.D., PAS features “abnormal, maladaptive behavior (refusal to have a relationship with a loving parent) that is driven by an abnormal mental state (the false belief that the rejected parent is evil, dangerous, or unworthy of love)” (J. Am. Acad. Psychiatry Law 2013;41:98-104). There is considered to be brainwashing of the child by one parent against the other parent in order to gain leverage in a court of law.

What is the mechanism in alienation? Enmeshment and overidentification of the child with the favored custodial parent is common. The child depends on this adult for his survival. The process of divorce can increase enmeshment with the custodial parent. The parent might reinforce the enmeshment by instilling fear of the “other” parent. The belief that the “other parent” is “bad” is transmitted through conscious and unconscious mechanisms.

The conscious mechanism is direct expression of anger toward the alienated parent. The anger might be motivated by rejection or as revenge for rejection with a desire to punish. The unconscious mechanisms include projective identification. In this situation, anger is seen as being embodied within the “other.” The projecting parent who continues to “hate” keeps the children tied to her out of projected fear of the “other.” The parent who uses projection is likely to have a primitive character structure. The child of the narcissistic custodial parent then acts out the shame and rage at the failure of the marriage.

These domestic tragedies have been around since the beginning of time. In Greek mythology, Medea, having been abandoned by Jason, took her revenge by murdering her two children. “Hell hath no fury like a woman scorned” is a paraphrase from William Congreve’s The Mourning Bride (1697).

What does the DSM-5 say?

Are these disorders and syndromes “real” psychiatric illnesses? The DSM-5 no longer separates delusional disorder from shared delusional disorder. If criteria are met for delusional disorder, that diagnosis is made. If the diagnosis cannot be made but shared beliefs are present, the diagnosis “other specified schizophrenia spectrum and other psychotic disorder” is used.

Those who advocated for inclusion of PAS cited the benefits that follow from a legitimate diagnosis such as legitimatizing problems that family therapists and psychotherapists encounter, allowing insurance coverage, and stimulating research. However, PAS was rejected as not having a good enough scientific basis.

Managing affective involvement

How does the psychiatrist manage families where emotional involvement is extreme? Psychiatrists first need to decide whether the family is capable of making changes and is willing to work on structural change within the family. If not, we can help patients remove themselves from destructive family situations. If the patient in your office wants to leave the family system or minimize the impact of the family system, individual psychotherapy that identifies the impact of family dysfunction, such as cognitive-behavioral therapy, can be used as a type of deprogramming. Exit strategies also can be discussed.

Al-Anon, for example, clarifies the influence of the family system on family members’ well-being by asking several questions, including:

Do you tell lies to cover up for someone else’s drinking?

Do you feel that if they cared about you, they would stop drinking to please you?

Do you make threats, such as, “If you don’t stop drinking, I’ll leave you?”

Are you afraid to upset someone for fear it will set off a drinking bout?

Have you considered calling the police for help in fear of abuse?

Do you feel like a failure because you can’t control the drinking?

Do you think that if they stopped drinking, your other problems would be solved?

If you think there is capacity for family change, the following strategies are helpful:

1. Education about appropriate differentiation

According to Dr. Murray Bowen, one of the main tasks of individuation is finding the right level of differentiation from parents. At one end of the differentiation spectrum is emotional fusion, and at the other end is emotional cutoff (disconnection between family members or refusal to engage with certain family members) (see “Family Evaluation,” New York: W.W. Norton & Co., 1988).

When family enmeshment is present, we can educate the family about individuation. In this way, the family develops a greater intellectual understanding of how they function, compared to their cultural norm. The family may benefit from creating a genogram that clarifies patterns of emotional involvement in their family of origin. Look for intergenerational patterns, and discuss how emotional differentiation occurred in prior generations. Teach the family about the emotional tasks of differentiation.

2. If there is alienation, parse out the reasons

Clarify conscious mechanisms that force the child to reject the other parent. Help the parent understand the consequences for the child in having no access to the other parent. Again, using a genogram helps identify intergenerational patterns, such as emotional cutoffs. Explore the reason for prior family emotional cutoffs. Identify typical patterns in the family for managing anger and conflicts.

In cases of divorce of the custodial parent, look at how anger is managed and stages of grief. Look for the presence of narcissistic injury. Discuss what a good divorce is and the healthiest way for the child to grow up. Help the parent manage and process her own affect without contaminating the child. It is not the role of the child to be the parental caregiver.

Help the child see that there was a loving relationship in the past and that new family goals can be created. The child also might experience anger and grief, and it is important to educate the child about how to manage those feelings appropriately rather than using blame and alienation. Help the child be empowered by positive ideals rather than negative emotions.

Psychiatrists often avoid working with these families, and perceive them as stuck and unable to change. This might be true for some families but certainly not all. Many families find themselves in situations that they do not understand and with problems they need help resolving. Educating and working with families who are stuck and who ask for and want change can change the life trajectory of many people.

Dr. Heru is with the department of psychiatry at the University of Colorado Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).