Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”

Thrombus

Credit: Kevin MacKenzie

Results of a phase 1 trial suggest the REG2 anticoagulation system can attenuate thrombin generation and then restore thrombin following reversal.

The REG2 system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen.

REG2 is formulated to provide a controllable level of anticoagulation for up to 2 weeks for sub-acute uses, especially in cases where a patient may be unable to swallow an oral anticoagulant.

Results observed with REG2 were published in the Journal of Thrombosis and Thrombolysis. The study was sponsored by Regado Biosciences, Inc, the company developing the REG2 system.

The study included 32 healthy volunteers who were enrolled sequentially into 4 cohorts. Patients in cohorts 1-3 were randomized (3:1) to ascending doses of pegnivacogin—from 0.5 mg/kg to 3 mg/kg—or placebo, with no anivamersen administered.

In cohort 4, all patients received 2 mg/kg of pegnivacogin and were randomized (1:1) to reversal by 1 dose or multiple doses over time of 1 mg/kg of anivamersen.

The researchers drew blood samples in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. They initiated thrombin generation with tissue factor and measured thrombin generation kinetics using the calibrated automated thrombogram (CAT).

The team found that REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose- and concentration-dependent response to pegnivacogin.

Specifically, there was a decrease in velocity index (VIx) from baseline to 24 hours after pegnivacogin administration. The largest percent change in VIx was in cohort 3 (3 mg/kg). There was a 90% decrease at 24 hours post-dose. This remained stable up to 48 hours in cohort 1 and up to 96 hours in cohorts 2 and 3.

Similarly, mean peak thrombin generation (PTG) values decreased as pegnivacogin dose and plasma concentrations increased. Cohort 3 had an 80% decrease in PTG at 24 hours post-dose. The percent change in mean PTG was consistent and preserved for at least 24 hours for all pegnivacogin doses. In cohorts 2 and 3, it was stable for at least 96 hours.

Endogenous thrombin potential (ETP) levels also decreased after pegnivacogin administration. Again, the largest decrease occurred in cohort 3, which exhibited a 65% decrease at 24 hours. Beyond that, the percent change in ETP was stable within each dose group, up to the last recorded measurement at 96 hours.

Peak time (PTm) was positively correlated with pegnivacogin concentration and relative activated partial thromboplastin time values. The correlation between PTm and quartile of pegnivacogin concentration was statistically significant (P=0.04) but weaker than that of ETP (P=0.001), PTG (P<0.001), or VIx (P<0.001). The changes in PTm persisted for at least 96 hours after pegnivacogin administration.

Finally, the researchers found that anivamersen reversed the effects of pegnivacogin, restoring thrombin generation without rebound effect.

Thrombus

Credit: Kevin MacKenzie

Results of a phase 1 trial suggest the REG2 anticoagulation system can attenuate thrombin generation and then restore thrombin following reversal.

The REG2 system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen.

REG2 is formulated to provide a controllable level of anticoagulation for up to 2 weeks for sub-acute uses, especially in cases where a patient may be unable to swallow an oral anticoagulant.

Results observed with REG2 were published in the Journal of Thrombosis and Thrombolysis. The study was sponsored by Regado Biosciences, Inc, the company developing the REG2 system.

The study included 32 healthy volunteers who were enrolled sequentially into 4 cohorts. Patients in cohorts 1-3 were randomized (3:1) to ascending doses of pegnivacogin—from 0.5 mg/kg to 3 mg/kg—or placebo, with no anivamersen administered.

In cohort 4, all patients received 2 mg/kg of pegnivacogin and were randomized (1:1) to reversal by 1 dose or multiple doses over time of 1 mg/kg of anivamersen.

The researchers drew blood samples in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. They initiated thrombin generation with tissue factor and measured thrombin generation kinetics using the calibrated automated thrombogram (CAT).

The team found that REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose- and concentration-dependent response to pegnivacogin.

Specifically, there was a decrease in velocity index (VIx) from baseline to 24 hours after pegnivacogin administration. The largest percent change in VIx was in cohort 3 (3 mg/kg). There was a 90% decrease at 24 hours post-dose. This remained stable up to 48 hours in cohort 1 and up to 96 hours in cohorts 2 and 3.

Similarly, mean peak thrombin generation (PTG) values decreased as pegnivacogin dose and plasma concentrations increased. Cohort 3 had an 80% decrease in PTG at 24 hours post-dose. The percent change in mean PTG was consistent and preserved for at least 24 hours for all pegnivacogin doses. In cohorts 2 and 3, it was stable for at least 96 hours.

Endogenous thrombin potential (ETP) levels also decreased after pegnivacogin administration. Again, the largest decrease occurred in cohort 3, which exhibited a 65% decrease at 24 hours. Beyond that, the percent change in ETP was stable within each dose group, up to the last recorded measurement at 96 hours.

Peak time (PTm) was positively correlated with pegnivacogin concentration and relative activated partial thromboplastin time values. The correlation between PTm and quartile of pegnivacogin concentration was statistically significant (P=0.04) but weaker than that of ETP (P=0.001), PTG (P<0.001), or VIx (P<0.001). The changes in PTm persisted for at least 96 hours after pegnivacogin administration.

Finally, the researchers found that anivamersen reversed the effects of pegnivacogin, restoring thrombin generation without rebound effect.

Thrombus

Credit: Kevin MacKenzie

Results of a phase 1 trial suggest the REG2 anticoagulation system can attenuate thrombin generation and then restore thrombin following reversal.

The REG2 system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen.

REG2 is formulated to provide a controllable level of anticoagulation for up to 2 weeks for sub-acute uses, especially in cases where a patient may be unable to swallow an oral anticoagulant.

Results observed with REG2 were published in the Journal of Thrombosis and Thrombolysis. The study was sponsored by Regado Biosciences, Inc, the company developing the REG2 system.

The study included 32 healthy volunteers who were enrolled sequentially into 4 cohorts. Patients in cohorts 1-3 were randomized (3:1) to ascending doses of pegnivacogin—from 0.5 mg/kg to 3 mg/kg—or placebo, with no anivamersen administered.

In cohort 4, all patients received 2 mg/kg of pegnivacogin and were randomized (1:1) to reversal by 1 dose or multiple doses over time of 1 mg/kg of anivamersen.

The researchers drew blood samples in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. They initiated thrombin generation with tissue factor and measured thrombin generation kinetics using the calibrated automated thrombogram (CAT).

The team found that REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose- and concentration-dependent response to pegnivacogin.

Specifically, there was a decrease in velocity index (VIx) from baseline to 24 hours after pegnivacogin administration. The largest percent change in VIx was in cohort 3 (3 mg/kg). There was a 90% decrease at 24 hours post-dose. This remained stable up to 48 hours in cohort 1 and up to 96 hours in cohorts 2 and 3.

Similarly, mean peak thrombin generation (PTG) values decreased as pegnivacogin dose and plasma concentrations increased. Cohort 3 had an 80% decrease in PTG at 24 hours post-dose. The percent change in mean PTG was consistent and preserved for at least 24 hours for all pegnivacogin doses. In cohorts 2 and 3, it was stable for at least 96 hours.

Endogenous thrombin potential (ETP) levels also decreased after pegnivacogin administration. Again, the largest decrease occurred in cohort 3, which exhibited a 65% decrease at 24 hours. Beyond that, the percent change in ETP was stable within each dose group, up to the last recorded measurement at 96 hours.

Peak time (PTm) was positively correlated with pegnivacogin concentration and relative activated partial thromboplastin time values. The correlation between PTm and quartile of pegnivacogin concentration was statistically significant (P=0.04) but weaker than that of ETP (P=0.001), PTG (P<0.001), or VIx (P<0.001). The changes in PTm persisted for at least 96 hours after pegnivacogin administration.

Finally, the researchers found that anivamersen reversed the effects of pegnivacogin, restoring thrombin generation without rebound effect.

Parenteral nutrition

Current guidelines to help prevent bloodstream infections during intravenous feeding may need revisions to strengthen protection for patients, a new study suggests.

These guidelines restrict how long a single bag of parenteral nutrition containing lipids can be used, due to the ability of lipids to encourage the growth of microorganisms.

But researchers found the guidelines do not account for other independent factors that can affect the growth of potentially deadly microorganisms.

Their findings appear in the Journal of Parenteral and Enteral Nutrition.

Peter David Austin, of the University of Southampton in the UK, and his colleagues looked at the growth of Escherichia coli and Enterococcus durans in parenteral nutrition to identify factors that can affect microbial growth.

They assessed the growth of E coli and E durans in quadruplicate in 12 different patients who received parenteral nutrition, with and without lipid, in varying glucose concentrations.

Results showed that glucose concentration, the proportion of glucose to lipid, and osmolarity all affected microbial growth, in addition to the presence of lipids.

The researchers therefore recommend these additional factors be considered when making clinical and policy decisions to limit the potential growth of microorganisms in parenteral nutrition.

Parenteral nutrition

Current guidelines to help prevent bloodstream infections during intravenous feeding may need revisions to strengthen protection for patients, a new study suggests.

These guidelines restrict how long a single bag of parenteral nutrition containing lipids can be used, due to the ability of lipids to encourage the growth of microorganisms.

But researchers found the guidelines do not account for other independent factors that can affect the growth of potentially deadly microorganisms.

Their findings appear in the Journal of Parenteral and Enteral Nutrition.

Peter David Austin, of the University of Southampton in the UK, and his colleagues looked at the growth of Escherichia coli and Enterococcus durans in parenteral nutrition to identify factors that can affect microbial growth.

They assessed the growth of E coli and E durans in quadruplicate in 12 different patients who received parenteral nutrition, with and without lipid, in varying glucose concentrations.

Results showed that glucose concentration, the proportion of glucose to lipid, and osmolarity all affected microbial growth, in addition to the presence of lipids.

The researchers therefore recommend these additional factors be considered when making clinical and policy decisions to limit the potential growth of microorganisms in parenteral nutrition.

Parenteral nutrition

Current guidelines to help prevent bloodstream infections during intravenous feeding may need revisions to strengthen protection for patients, a new study suggests.

These guidelines restrict how long a single bag of parenteral nutrition containing lipids can be used, due to the ability of lipids to encourage the growth of microorganisms.

But researchers found the guidelines do not account for other independent factors that can affect the growth of potentially deadly microorganisms.

Their findings appear in the Journal of Parenteral and Enteral Nutrition.

Peter David Austin, of the University of Southampton in the UK, and his colleagues looked at the growth of Escherichia coli and Enterococcus durans in parenteral nutrition to identify factors that can affect microbial growth.

They assessed the growth of E coli and E durans in quadruplicate in 12 different patients who received parenteral nutrition, with and without lipid, in varying glucose concentrations.

Results showed that glucose concentration, the proportion of glucose to lipid, and osmolarity all affected microbial growth, in addition to the presence of lipids.

The researchers therefore recommend these additional factors be considered when making clinical and policy decisions to limit the potential growth of microorganisms in parenteral nutrition.