Adult brain tumor survivors taking donepezil, a drug approved for the treatment of Alzheimer’s disease, showed significant improvements in the cognitive functions of memory, motor speed, and dexterity, compared with those taking a placebo. However, improvements in the primary outcome of composite cognitive function were similar for the two arms, investigators reported.

The study results were published online April 20 in the Journal of Clinical Oncology.

istock/Thinkstock

Patients with greater pretreatment deficits saw greater improvements in cognitive functioning with donepezil treatment, reported Stephen Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest School of Medicine, Winston-Salem, N.C., and associates.

“This suggests that treatment with a daily dose of donepezil can provide benefit to some adult long-term brain tumor survivors after PBI or WBI [partial- or whole-brain irradiation], particularly those with greater pretreatment cognitive impairment,” they wrote (J. Clin. Oncol. 2015 Apr. 20 [doi: 10.1200/JCO.2014.58.4508]).

The phase III trial enrolled 198 primary or metastatic brain tumor survivors who underwent fractionated PBI or WBI at least 6 months previously. Patients received either donepezil at 5 mg daily for 6 weeks, followed by 10 mg daily for 18 weeks if well tolerated, or placebo for 24 weeks. Composite cognitive scores improved for both arms and did not differ significantly. Donepezil treatment resulted in significantly greater improvements in memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016).

Donepezil was generally well tolerated, except for diarrhea in 25% of the active arm vs. 9% in the placebo arm (P = .005). The study retention rate was 74% at 24 weeks for both groups.

Although enrolled patients had a high level of cognitive impairment relative to noncancer controls, with 91% having at least one test score at least 1.5 standard deviations below the normal comparison group, scores across most measures varied widely from significantly lower to higher than the comparison group. This heterogeneity may underlie the less than significant improvement observed with the study treatment. Patients with greater cognitive deficits saw greater benefits.

“This indicates that brain tumors and their treatments, including cranial irradiation, are associated with clinically significant cognitive impairment among some but not all patients. In future studies, demonstrable cognitive impairment should be an inclusion criterion for enrollment,” Dr. Rapp and associates wrote.

Adult brain tumor survivors taking donepezil, a drug approved for the treatment of Alzheimer’s disease, showed significant improvements in the cognitive functions of memory, motor speed, and dexterity, compared with those taking a placebo. However, improvements in the primary outcome of composite cognitive function were similar for the two arms, investigators reported.

The study results were published online April 20 in the Journal of Clinical Oncology.

istock/Thinkstock

Patients with greater pretreatment deficits saw greater improvements in cognitive functioning with donepezil treatment, reported Stephen Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest School of Medicine, Winston-Salem, N.C., and associates.

“This suggests that treatment with a daily dose of donepezil can provide benefit to some adult long-term brain tumor survivors after PBI or WBI [partial- or whole-brain irradiation], particularly those with greater pretreatment cognitive impairment,” they wrote (J. Clin. Oncol. 2015 Apr. 20 [doi: 10.1200/JCO.2014.58.4508]).

The phase III trial enrolled 198 primary or metastatic brain tumor survivors who underwent fractionated PBI or WBI at least 6 months previously. Patients received either donepezil at 5 mg daily for 6 weeks, followed by 10 mg daily for 18 weeks if well tolerated, or placebo for 24 weeks. Composite cognitive scores improved for both arms and did not differ significantly. Donepezil treatment resulted in significantly greater improvements in memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016).

Donepezil was generally well tolerated, except for diarrhea in 25% of the active arm vs. 9% in the placebo arm (P = .005). The study retention rate was 74% at 24 weeks for both groups.

Although enrolled patients had a high level of cognitive impairment relative to noncancer controls, with 91% having at least one test score at least 1.5 standard deviations below the normal comparison group, scores across most measures varied widely from significantly lower to higher than the comparison group. This heterogeneity may underlie the less than significant improvement observed with the study treatment. Patients with greater cognitive deficits saw greater benefits.

“This indicates that brain tumors and their treatments, including cranial irradiation, are associated with clinically significant cognitive impairment among some but not all patients. In future studies, demonstrable cognitive impairment should be an inclusion criterion for enrollment,” Dr. Rapp and associates wrote.

Adult brain tumor survivors taking donepezil, a drug approved for the treatment of Alzheimer’s disease, showed significant improvements in the cognitive functions of memory, motor speed, and dexterity, compared with those taking a placebo. However, improvements in the primary outcome of composite cognitive function were similar for the two arms, investigators reported.

The study results were published online April 20 in the Journal of Clinical Oncology.

istock/Thinkstock

Patients with greater pretreatment deficits saw greater improvements in cognitive functioning with donepezil treatment, reported Stephen Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest School of Medicine, Winston-Salem, N.C., and associates.

“This suggests that treatment with a daily dose of donepezil can provide benefit to some adult long-term brain tumor survivors after PBI or WBI [partial- or whole-brain irradiation], particularly those with greater pretreatment cognitive impairment,” they wrote (J. Clin. Oncol. 2015 Apr. 20 [doi: 10.1200/JCO.2014.58.4508]).

The phase III trial enrolled 198 primary or metastatic brain tumor survivors who underwent fractionated PBI or WBI at least 6 months previously. Patients received either donepezil at 5 mg daily for 6 weeks, followed by 10 mg daily for 18 weeks if well tolerated, or placebo for 24 weeks. Composite cognitive scores improved for both arms and did not differ significantly. Donepezil treatment resulted in significantly greater improvements in memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016).

Donepezil was generally well tolerated, except for diarrhea in 25% of the active arm vs. 9% in the placebo arm (P = .005). The study retention rate was 74% at 24 weeks for both groups.

Although enrolled patients had a high level of cognitive impairment relative to noncancer controls, with 91% having at least one test score at least 1.5 standard deviations below the normal comparison group, scores across most measures varied widely from significantly lower to higher than the comparison group. This heterogeneity may underlie the less than significant improvement observed with the study treatment. Patients with greater cognitive deficits saw greater benefits.

“This indicates that brain tumors and their treatments, including cranial irradiation, are associated with clinically significant cognitive impairment among some but not all patients. In future studies, demonstrable cognitive impairment should be an inclusion criterion for enrollment,” Dr. Rapp and associates wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).

Two changes in the pharmaceutical market in late 2010 dramatically reversed the alarming rise in fatal opioid overdoses that occurred during the preceding decade, according to a report published online April 20 in JAMA Internal Medicine.

Overdose deaths attributed to prescription opioids quadrupled in the U.S. between 1999 and 2010, in parallel with rapidly expanding sales of the drugs. Two changes in the pharmaceutical market were undertaken to address these unrelenting increases: replacing the standard formulation of OxyContin with an abuse-deterrent formulation (resistant to crushing and dissolving the tablets for ingestion, snorting, or injection) and withdrawing propoxyphene from sale, wrote Dr. Marc R. Larochelle of Harvard Pilgrim Health Care Institute and the department of population medicine, Harvard, both in Boston, and his associates.

To assess the impact of these 2 interventions, the investigators examined hospitalizations for prescription opioids as well as dispensing patterns using an insurance database covering adults in all 50 states. The data comprised 31,316,598 patients aged 18-64 who were enrolled in a commercial health plan between 2003 and 2012. There were 12,164 overdoses attributed to prescription opioids during the study period.

The “sudden, substantial, and sustained decreases” in the dispensing of prescription opioids at the end of 2010 was associated with parallel declines in fatal overdoses, which dropped by 19% in 2011 and by a further 20% in 2012. “Extrapolating our estimates at 2 years to the 124 million commercially insured U.S. residents aged 18-64 years, there would be 5,456 fewer prescription opioid overdoses . . . annually,” Dr. Larochelle and his associates said (JAMA Intern. Med. 2015 April 20 [doi:10.1001/jamainternmed.2015.0914]).

“This is the first study to demonstrate that a decrease in opioid supply is associated with a decrease in overall prescription opioid overdose,” they noted. “Our results have significant implications for policymakers and health care professionals grappling with the epidemic of opioid abuse and overdose.”

Two changes in the pharmaceutical market in late 2010 dramatically reversed the alarming rise in fatal opioid overdoses that occurred during the preceding decade, according to a report published online April 20 in JAMA Internal Medicine.

Overdose deaths attributed to prescription opioids quadrupled in the U.S. between 1999 and 2010, in parallel with rapidly expanding sales of the drugs. Two changes in the pharmaceutical market were undertaken to address these unrelenting increases: replacing the standard formulation of OxyContin with an abuse-deterrent formulation (resistant to crushing and dissolving the tablets for ingestion, snorting, or injection) and withdrawing propoxyphene from sale, wrote Dr. Marc R. Larochelle of Harvard Pilgrim Health Care Institute and the department of population medicine, Harvard, both in Boston, and his associates.

To assess the impact of these 2 interventions, the investigators examined hospitalizations for prescription opioids as well as dispensing patterns using an insurance database covering adults in all 50 states. The data comprised 31,316,598 patients aged 18-64 who were enrolled in a commercial health plan between 2003 and 2012. There were 12,164 overdoses attributed to prescription opioids during the study period.

The “sudden, substantial, and sustained decreases” in the dispensing of prescription opioids at the end of 2010 was associated with parallel declines in fatal overdoses, which dropped by 19% in 2011 and by a further 20% in 2012. “Extrapolating our estimates at 2 years to the 124 million commercially insured U.S. residents aged 18-64 years, there would be 5,456 fewer prescription opioid overdoses . . . annually,” Dr. Larochelle and his associates said (JAMA Intern. Med. 2015 April 20 [doi:10.1001/jamainternmed.2015.0914]).

“This is the first study to demonstrate that a decrease in opioid supply is associated with a decrease in overall prescription opioid overdose,” they noted. “Our results have significant implications for policymakers and health care professionals grappling with the epidemic of opioid abuse and overdose.”

Two changes in the pharmaceutical market in late 2010 dramatically reversed the alarming rise in fatal opioid overdoses that occurred during the preceding decade, according to a report published online April 20 in JAMA Internal Medicine.

Overdose deaths attributed to prescription opioids quadrupled in the U.S. between 1999 and 2010, in parallel with rapidly expanding sales of the drugs. Two changes in the pharmaceutical market were undertaken to address these unrelenting increases: replacing the standard formulation of OxyContin with an abuse-deterrent formulation (resistant to crushing and dissolving the tablets for ingestion, snorting, or injection) and withdrawing propoxyphene from sale, wrote Dr. Marc R. Larochelle of Harvard Pilgrim Health Care Institute and the department of population medicine, Harvard, both in Boston, and his associates.

To assess the impact of these 2 interventions, the investigators examined hospitalizations for prescription opioids as well as dispensing patterns using an insurance database covering adults in all 50 states. The data comprised 31,316,598 patients aged 18-64 who were enrolled in a commercial health plan between 2003 and 2012. There were 12,164 overdoses attributed to prescription opioids during the study period.

The “sudden, substantial, and sustained decreases” in the dispensing of prescription opioids at the end of 2010 was associated with parallel declines in fatal overdoses, which dropped by 19% in 2011 and by a further 20% in 2012. “Extrapolating our estimates at 2 years to the 124 million commercially insured U.S. residents aged 18-64 years, there would be 5,456 fewer prescription opioid overdoses . . . annually,” Dr. Larochelle and his associates said (JAMA Intern. Med. 2015 April 20 [doi:10.1001/jamainternmed.2015.0914]).

“This is the first study to demonstrate that a decrease in opioid supply is associated with a decrease in overall prescription opioid overdose,” they noted. “Our results have significant implications for policymakers and health care professionals grappling with the epidemic of opioid abuse and overdose.”

An EBV-infected cell (green)

among uninfected cells (blue)

Image courtesy of NIH/

Benjamin Chaigne-Delalande

PHILADELPHIA—Cytotoxic T lymphocytes designed to target Epstein-Barr virus (EBV-CTLs) can elicit durable responses in patients

with EBV–associated lymphoproliferative disorder (EBV-LPD), according to data presented at the AACRAnnual Meeting 2015.

Results from two trials showed that EBV-CTLs derived from a patient’s transplant donor could produce a response rate of 62%, and EBV-CTLs derived from third-party donors could produce a response rate of 61%.

Study investigators noted that, with the achievement of complete response (CR), remission proved durable. And, unlike with chemotherapy, partial responses (PRs) to EBV-CTLs were durable as well.

The team presented these results as abstract CT107.*

“The purpose of our clinical trials was to see if giving T cells from a normal-immune individual that were expanded in culture and stimulated to respond to multiple proteins from the Epstein-Barr virus could provide a safe and effective treatment,” said Richard J. O’Reilly, MD, of Memorial Sloan Kettering Cancer Center in New York.

“The good news from our two clinical trials is that EBV-CTLs generated from either the patient’s transplant donor or from the bank of normal donor T cells developed at Memorial Sloan Kettering put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60% of patients.”

In the first trial, 26 patients with EBV-LPD received EBV-CTLs generated from their transplant donor. Thirteen of these patients had previously received rituximab, and 16 had high-risk disease.

Thirteen patients in this trial received HLA-matched, EBV-CTLs from the Memorial Sloan Kettering Cancer Center bank of EBV-CTLs generated from third-party, healthy donors. All 13 patients had high-risk disease, and 12 had received prior rituximab.

Dr O’Reilly noted that good results were observed with EBV-CTLs from both sources in this trial. And because EBV-CTLs from the bank are available immediately, he and his team used only EBV-CTLs from the bank when treating the 18 patients enrolled in the second trial.

Among the 39 patients enrolled in the first trial, 23 had a CR, none had a PR, and 2 had stable disease.

For patients who received EBV-CTLs from their primary donor, the combined rate of CR and PR was 62% (16 CRs). For patients who received third-party EBV-CTLs, the combined rate of CR and PR was 54% (7 CRs).

Sixteen of the patients who achieved a CR are still doing well, Dr O’Reilly said. Eight of these patients are alive more than 5 years after receiving EBV-CTLs, and 1 is alive more than 10 years after treatment.

Among the 18 patients enrolled in the second trial, 9 had a CR, 3 had a PR, and 1 had stable disease. The combined rate of CR and PR was 67%.

All of the patients who achieved a CR in this trial continue to do well, and the investigators will be following them long-term, Dr O’Reilly said.

He also noted that toxicities with EBV-CTLs were minimal, and there were no treatment-related deaths. None of the patients developed cytokine release syndrome or graft-vs-host disease requiring systemic therapy.

“The EBV-CTLs work well for the majority of recipients,” Dr O’Reilly said. “However, the responses became clinically evident only after the T cells expanded in vivo, which took about 7 to 14 days. We are rigorously pursuing the development of biomarkers or other tests to predict response earlier.”

Memorial Sloan Kettering Cancer Center has entered into an option agreement with Atara Biotherapeutics to further develop EBV-CTLs for clinical use. However, the data presented at AACR were accrued prior to that agreement.

Last month, the US Food and Drug Administration granted breakthrough therapy designation to EBV-CTLs generated from third-party donors for the treatment of patients with rituximab-refractory EBV-LPD.

*Information in the abstract differs from that presented at the meeting. 

An EBV-infected cell (green)

among uninfected cells (blue)

Image courtesy of NIH/

Benjamin Chaigne-Delalande

PHILADELPHIA—Cytotoxic T lymphocytes designed to target Epstein-Barr virus (EBV-CTLs) can elicit durable responses in patients

with EBV–associated lymphoproliferative disorder (EBV-LPD), according to data presented at the AACRAnnual Meeting 2015.

Results from two trials showed that EBV-CTLs derived from a patient’s transplant donor could produce a response rate of 62%, and EBV-CTLs derived from third-party donors could produce a response rate of 61%.

Study investigators noted that, with the achievement of complete response (CR), remission proved durable. And, unlike with chemotherapy, partial responses (PRs) to EBV-CTLs were durable as well.

The team presented these results as abstract CT107.*

“The purpose of our clinical trials was to see if giving T cells from a normal-immune individual that were expanded in culture and stimulated to respond to multiple proteins from the Epstein-Barr virus could provide a safe and effective treatment,” said Richard J. O’Reilly, MD, of Memorial Sloan Kettering Cancer Center in New York.

“The good news from our two clinical trials is that EBV-CTLs generated from either the patient’s transplant donor or from the bank of normal donor T cells developed at Memorial Sloan Kettering put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60% of patients.”

In the first trial, 26 patients with EBV-LPD received EBV-CTLs generated from their transplant donor. Thirteen of these patients had previously received rituximab, and 16 had high-risk disease.

Thirteen patients in this trial received HLA-matched, EBV-CTLs from the Memorial Sloan Kettering Cancer Center bank of EBV-CTLs generated from third-party, healthy donors. All 13 patients had high-risk disease, and 12 had received prior rituximab.

Dr O’Reilly noted that good results were observed with EBV-CTLs from both sources in this trial. And because EBV-CTLs from the bank are available immediately, he and his team used only EBV-CTLs from the bank when treating the 18 patients enrolled in the second trial.

Among the 39 patients enrolled in the first trial, 23 had a CR, none had a PR, and 2 had stable disease.

For patients who received EBV-CTLs from their primary donor, the combined rate of CR and PR was 62% (16 CRs). For patients who received third-party EBV-CTLs, the combined rate of CR and PR was 54% (7 CRs).

Sixteen of the patients who achieved a CR are still doing well, Dr O’Reilly said. Eight of these patients are alive more than 5 years after receiving EBV-CTLs, and 1 is alive more than 10 years after treatment.

Among the 18 patients enrolled in the second trial, 9 had a CR, 3 had a PR, and 1 had stable disease. The combined rate of CR and PR was 67%.

All of the patients who achieved a CR in this trial continue to do well, and the investigators will be following them long-term, Dr O’Reilly said.

He also noted that toxicities with EBV-CTLs were minimal, and there were no treatment-related deaths. None of the patients developed cytokine release syndrome or graft-vs-host disease requiring systemic therapy.

“The EBV-CTLs work well for the majority of recipients,” Dr O’Reilly said. “However, the responses became clinically evident only after the T cells expanded in vivo, which took about 7 to 14 days. We are rigorously pursuing the development of biomarkers or other tests to predict response earlier.”

Memorial Sloan Kettering Cancer Center has entered into an option agreement with Atara Biotherapeutics to further develop EBV-CTLs for clinical use. However, the data presented at AACR were accrued prior to that agreement.

Last month, the US Food and Drug Administration granted breakthrough therapy designation to EBV-CTLs generated from third-party donors for the treatment of patients with rituximab-refractory EBV-LPD.

*Information in the abstract differs from that presented at the meeting. 

An EBV-infected cell (green)

among uninfected cells (blue)

Image courtesy of NIH/

Benjamin Chaigne-Delalande

PHILADELPHIA—Cytotoxic T lymphocytes designed to target Epstein-Barr virus (EBV-CTLs) can elicit durable responses in patients

with EBV–associated lymphoproliferative disorder (EBV-LPD), according to data presented at the AACRAnnual Meeting 2015.

Results from two trials showed that EBV-CTLs derived from a patient’s transplant donor could produce a response rate of 62%, and EBV-CTLs derived from third-party donors could produce a response rate of 61%.

Study investigators noted that, with the achievement of complete response (CR), remission proved durable. And, unlike with chemotherapy, partial responses (PRs) to EBV-CTLs were durable as well.

The team presented these results as abstract CT107.*

“The purpose of our clinical trials was to see if giving T cells from a normal-immune individual that were expanded in culture and stimulated to respond to multiple proteins from the Epstein-Barr virus could provide a safe and effective treatment,” said Richard J. O’Reilly, MD, of Memorial Sloan Kettering Cancer Center in New York.

“The good news from our two clinical trials is that EBV-CTLs generated from either the patient’s transplant donor or from the bank of normal donor T cells developed at Memorial Sloan Kettering put aggressive EBV-LPD that had failed to respond to rituximab into long-lasting remission in more than 60% of patients.”

In the first trial, 26 patients with EBV-LPD received EBV-CTLs generated from their transplant donor. Thirteen of these patients had previously received rituximab, and 16 had high-risk disease.

Thirteen patients in this trial received HLA-matched, EBV-CTLs from the Memorial Sloan Kettering Cancer Center bank of EBV-CTLs generated from third-party, healthy donors. All 13 patients had high-risk disease, and 12 had received prior rituximab.

Dr O’Reilly noted that good results were observed with EBV-CTLs from both sources in this trial. And because EBV-CTLs from the bank are available immediately, he and his team used only EBV-CTLs from the bank when treating the 18 patients enrolled in the second trial.

Among the 39 patients enrolled in the first trial, 23 had a CR, none had a PR, and 2 had stable disease.

For patients who received EBV-CTLs from their primary donor, the combined rate of CR and PR was 62% (16 CRs). For patients who received third-party EBV-CTLs, the combined rate of CR and PR was 54% (7 CRs).

Sixteen of the patients who achieved a CR are still doing well, Dr O’Reilly said. Eight of these patients are alive more than 5 years after receiving EBV-CTLs, and 1 is alive more than 10 years after treatment.

Among the 18 patients enrolled in the second trial, 9 had a CR, 3 had a PR, and 1 had stable disease. The combined rate of CR and PR was 67%.

All of the patients who achieved a CR in this trial continue to do well, and the investigators will be following them long-term, Dr O’Reilly said.

He also noted that toxicities with EBV-CTLs were minimal, and there were no treatment-related deaths. None of the patients developed cytokine release syndrome or graft-vs-host disease requiring systemic therapy.

“The EBV-CTLs work well for the majority of recipients,” Dr O’Reilly said. “However, the responses became clinically evident only after the T cells expanded in vivo, which took about 7 to 14 days. We are rigorously pursuing the development of biomarkers or other tests to predict response earlier.”

Memorial Sloan Kettering Cancer Center has entered into an option agreement with Atara Biotherapeutics to further develop EBV-CTLs for clinical use. However, the data presented at AACR were accrued prior to that agreement.

Last month, the US Food and Drug Administration granted breakthrough therapy designation to EBV-CTLs generated from third-party donors for the treatment of patients with rituximab-refractory EBV-LPD.

*Information in the abstract differs from that presented at the meeting. 

Mark Cragg, PhD

Photo courtesy of the

University of Southampton

A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.

Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.

But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.

In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.

“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.

“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”

In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.

In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.

In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.

In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.

Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.

The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.

Mark Cragg, PhD

Photo courtesy of the

University of Southampton

A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.

Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.

But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.

In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.

“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.

“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”

In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.

In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.

In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.

In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.

Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.

The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.

Mark Cragg, PhD

Photo courtesy of the

University of Southampton

A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.

Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.

But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.

In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.

“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.

“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”

In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.

In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.

In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.

In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.

Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.

The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.

For children as young as 2 years old, interventions such as behavioral therapy, flavored throat spray, a specialized pill cup, simple verbal instructions, and head-posture training were successful in improving pill swallowing abilities for more than half of the study population, according to the results of a data review published in Pediatrics.

Amee Patel, M.P.H., and her associates at the University of North Carolina at Chapel Hill, examined data from 211 articles identified in a PubMed search published between December 1986 and December 2013. Four cohort studies and one case series met the criteria for inclusion. Each of the studies concluded that pill acceptance rates were improved shortly after their intervention, with three studies reporting pill acceptance continuing for 3-6 months after the intervention.

“A major reason for the success of all the interventions is that every study recognized and specifically addressed problems with pill swallowing. As a result, there was a conscious effort to help children with their difficulties in swallowing pills,” the investigators wrote.

Read the entire article here: Pediatrics 2015 (doi: 10.1542/peds.2014-2114).

For children as young as 2 years old, interventions such as behavioral therapy, flavored throat spray, a specialized pill cup, simple verbal instructions, and head-posture training were successful in improving pill swallowing abilities for more than half of the study population, according to the results of a data review published in Pediatrics.

Amee Patel, M.P.H., and her associates at the University of North Carolina at Chapel Hill, examined data from 211 articles identified in a PubMed search published between December 1986 and December 2013. Four cohort studies and one case series met the criteria for inclusion. Each of the studies concluded that pill acceptance rates were improved shortly after their intervention, with three studies reporting pill acceptance continuing for 3-6 months after the intervention.

“A major reason for the success of all the interventions is that every study recognized and specifically addressed problems with pill swallowing. As a result, there was a conscious effort to help children with their difficulties in swallowing pills,” the investigators wrote.

Read the entire article here: Pediatrics 2015 (doi: 10.1542/peds.2014-2114).

For children as young as 2 years old, interventions such as behavioral therapy, flavored throat spray, a specialized pill cup, simple verbal instructions, and head-posture training were successful in improving pill swallowing abilities for more than half of the study population, according to the results of a data review published in Pediatrics.

Amee Patel, M.P.H., and her associates at the University of North Carolina at Chapel Hill, examined data from 211 articles identified in a PubMed search published between December 1986 and December 2013. Four cohort studies and one case series met the criteria for inclusion. Each of the studies concluded that pill acceptance rates were improved shortly after their intervention, with three studies reporting pill acceptance continuing for 3-6 months after the intervention.

“A major reason for the success of all the interventions is that every study recognized and specifically addressed problems with pill swallowing. As a result, there was a conscious effort to help children with their difficulties in swallowing pills,” the investigators wrote.

Read the entire article here: Pediatrics 2015 (doi: 10.1542/peds.2014-2114).

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.