Globally, new HIV infections have declined by just 18% in the past 7 years, but the decline is not quick enough to reach the United Nations’ target goal of reduced deaths and infections by 2020, according to a warning issued by UNAIDS in its July 2018 AIDS update report, Miles to Go: Closing gaps, breaking barriers, righting injustices.

“We are sounding the alarm. Entire regions are falling behind, the huge gains we made for children are not being sustained, women are still most affected, resources are still not matching political commitments, and key populations continue to be ignored,” Michel Sidibé, executive director of UNAIDS, said in a press release.

Even though almost 60% of the 36.9 million people living with HIV were on treatment in 2017, to reach the 30 million target an annual increase of 2.8 million people is required, and indications are that the rate of scale-up is slowing down, according to the report.

MattZ90/Thinkstock.com

[email protected]

Globally, new HIV infections have declined by just 18% in the past 7 years, but the decline is not quick enough to reach the United Nations’ target goal of reduced deaths and infections by 2020, according to a warning issued by UNAIDS in its July 2018 AIDS update report, Miles to Go: Closing gaps, breaking barriers, righting injustices.

“We are sounding the alarm. Entire regions are falling behind, the huge gains we made for children are not being sustained, women are still most affected, resources are still not matching political commitments, and key populations continue to be ignored,” Michel Sidibé, executive director of UNAIDS, said in a press release.

Even though almost 60% of the 36.9 million people living with HIV were on treatment in 2017, to reach the 30 million target an annual increase of 2.8 million people is required, and indications are that the rate of scale-up is slowing down, according to the report.

MattZ90/Thinkstock.com

[email protected]

Globally, new HIV infections have declined by just 18% in the past 7 years, but the decline is not quick enough to reach the United Nations’ target goal of reduced deaths and infections by 2020, according to a warning issued by UNAIDS in its July 2018 AIDS update report, Miles to Go: Closing gaps, breaking barriers, righting injustices.

“We are sounding the alarm. Entire regions are falling behind, the huge gains we made for children are not being sustained, women are still most affected, resources are still not matching political commitments, and key populations continue to be ignored,” Michel Sidibé, executive director of UNAIDS, said in a press release.

Even though almost 60% of the 36.9 million people living with HIV were on treatment in 2017, to reach the 30 million target an annual increase of 2.8 million people is required, and indications are that the rate of scale-up is slowing down, according to the report.

MattZ90/Thinkstock.com

[email protected]

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

Physicians from Menoufia University and Cairo University in Egypt, and Al Hada Armed Forces Hospital in Saudi Arabia report on a patient who developed myelodysplasia with excess blasts 1 year after he started on the tumor necrosis factor-alpha blocker etanercept for psoriasis. The patient, a 76-year-old man, arrived at the emergency department (ED) with ecchymosis and recurrent epistaxis. He had a critically low platelet count, anemia, and normal leukocyte count. The reticulocyte index, serum ferritin, and folate levels indicated ineffective erythropoiesis. Bone marrow aspirate and biopsy confirmed a diagnosis of myelodysplastic syndrome.

The physicians stopped the etanercept and administered 2 cycles of azacitidine and folic acid supplementation, but the response was minima,l and the patient platelet count worsened. While waiting for the third cycle, the patient was readmitted to the ED with lower gastrointestinal bleeding, epistaxis, and shock. He died of cardiopulmonary arrest.

The physicians note that immune dysregulation and altered T-cell hemostasis are essential to the development of myelodysplastic syndrome. They also note that nonspecific activation and proliferation of T lymphocytes has been documented as promoting epidermal growth in genetically susceptible psoriasis patients.

Myelodysplastic syndrome has been associated with psoriasis in about 7% of cases, and researchers have found a higher incidence of leukemia and laryngeal cancer in families of psoriasis patients. There also have been reports of leukemia in psoriasis patients on systemic immunosuppressives. Etanercept has various hematologic adverse effects, including pancytopenia and aplastic anemia.

However, only 4 cases (including this one) have been reported of myelodysplastic syndrome in psoriasis patients. Taken together, the cases add to the growing evidence that suggests a link between myelodysplastic syndrome and etanercept treatment for psoriasis. Those patients, the physicians caution, should be considered at dual risk from treatment and disease. The physicians also recommend regular routine blood counts and discontinuing etanercept at onset of any cytopenias.

Source:
Dawoud NM, Ayoub OH, Essa ES, Dawoud DM. Indian J Dermatol Venereol Leprol. 2018;84(4):463-465.
doi: 10.4103/ijdvl.IJDVL_463_17

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo by Cristina Granados

Receiving a plasma transfusion during emergency air transport can improve survival for trauma patients, according to a study published in NEJM.

Trauma patients with severe bleeding had a significant decrease in 30-day mortality when they received a plasma transfusion while being airlifted to a hospital.

Transfusion-related reactions and allergic reactions were more common among plasma recipients than patients who only received standard care.

However, this difference was not significant, and most of these reactions were considered minor.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” said study author Jason Sperry, MD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

Patients and intervention

This trial, known as PAMPer (Prehospital Air Medical Plasma), was a phase 3, randomized study enrolling 501 trauma patients at risk of hemorrhagic shock.

Most patients were male (72.7%), and most had suffered blunt trauma (82.4%). About half of patients (51.1%) had prehospital intubation, and more than a third (34.7%) received a prehospital transfusion of red blood cells.

Air medical bases participating in this study were randomized to administer plasma or standard care to eligible patients for 1-month intervals. When the air transport teams were in their plasma interval, they’d begin administering 2 units of thawed plasma to a patient as soon as trial eligibility was confirmed.

If the 2 units were completed during the flight, the team would revert to standard care. If the transfusions weren’t completed, the plasma would continue to be administered when the patient arrived at the trauma center.

The teams administered the assigned treatment 99% of the time (496/501).

In the plasma group, there were 205 patients (89.1%) who received 2 units of plasma, 21 (9.1%) who received 1 unit, and 4 patients (1.7%) who did not receive plasma due to logistical challenges.

In 84.4% of the patients, the plasma infusion was completed during air transport. The remaining patients completed their plasma transfusions at the trauma center.

There was 1 patient (0.4%) in the standard-care group who received plasma before transport began.

Primary outcome

The study’s primary outcome was 30-day mortality. Ninety-six percent of patients (n=481) had data for this outcome—220 patients in the plasma group and 261 in the standard-care group.

Thirty-day mortality was significantly lower in the plasma group than the standard-care group—23.2% and 33.0%, respectively (P=0.03).

In an adjusted analysis, the administration of prehospital plasma was associated with a 39% lower risk for 30-day mortality than standard care (adjusted odds ratio, 0.61; P=0.02).

Secondary outcomes

Initially, there were significant differences between the plasma (n=230) and standard-care groups (n=271) when it came to:

• Mortality at 24 hours—13.9% and 22.1%, respectively (P=0.02)
• In-hospital mortality—22.2% and 32.5%, respectively (P=0.01)
• Median volume of blood components transfused in the first 24 hours—3 and 4 units, respectively (P=0.02)
• Median volume of red cells transfused in the first 24 hours—3 and 4 units, respectively (P=0.03).
• Median prothrombin-time ratio at first blood sampling—1.2 and 1.3, respectively (P<0.001).

When the researchers adjusted P values for multiple comparisons, the between-group difference in prothrombin-time ratio remained significant (P<0.001).

However, the differences in 24-hour mortality (P=0.55), in-hospital mortality (P=0.33), blood components transfused (P=0.41), and red cells transfused (P=0.69) did not retain significance.

Likewise, there were no significant between-group differences (in adjusted or unadjusted analyses) when it came to multi-organ failure, acute lung injury/acute respiratory distress syndrome, nosocomial infections, or allergic/transfusion-related reactions.

There were 10 adverse events (AEs) considered related to the trial regimen. In the standard-care group, the 4 AEs were sepsis (a serious AE), adult respiratory distress syndrome (a serious AE), fever, and pain.

In the plasma group, the 6 AEs were 2 allergic reactions, 1 case of anaphylaxis, 1 case of hypotension, 1 case of urticaria, and 1 transfusion-related reaction (a serious AE).

Photo by Cristina Granados

Receiving a plasma transfusion during emergency air transport can improve survival for trauma patients, according to a study published in NEJM.

Trauma patients with severe bleeding had a significant decrease in 30-day mortality when they received a plasma transfusion while being airlifted to a hospital.

Transfusion-related reactions and allergic reactions were more common among plasma recipients than patients who only received standard care.

However, this difference was not significant, and most of these reactions were considered minor.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” said study author Jason Sperry, MD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

Patients and intervention

This trial, known as PAMPer (Prehospital Air Medical Plasma), was a phase 3, randomized study enrolling 501 trauma patients at risk of hemorrhagic shock.

Most patients were male (72.7%), and most had suffered blunt trauma (82.4%). About half of patients (51.1%) had prehospital intubation, and more than a third (34.7%) received a prehospital transfusion of red blood cells.

Air medical bases participating in this study were randomized to administer plasma or standard care to eligible patients for 1-month intervals. When the air transport teams were in their plasma interval, they’d begin administering 2 units of thawed plasma to a patient as soon as trial eligibility was confirmed.

If the 2 units were completed during the flight, the team would revert to standard care. If the transfusions weren’t completed, the plasma would continue to be administered when the patient arrived at the trauma center.

The teams administered the assigned treatment 99% of the time (496/501).

In the plasma group, there were 205 patients (89.1%) who received 2 units of plasma, 21 (9.1%) who received 1 unit, and 4 patients (1.7%) who did not receive plasma due to logistical challenges.

In 84.4% of the patients, the plasma infusion was completed during air transport. The remaining patients completed their plasma transfusions at the trauma center.

There was 1 patient (0.4%) in the standard-care group who received plasma before transport began.

Primary outcome

The study’s primary outcome was 30-day mortality. Ninety-six percent of patients (n=481) had data for this outcome—220 patients in the plasma group and 261 in the standard-care group.

Thirty-day mortality was significantly lower in the plasma group than the standard-care group—23.2% and 33.0%, respectively (P=0.03).

In an adjusted analysis, the administration of prehospital plasma was associated with a 39% lower risk for 30-day mortality than standard care (adjusted odds ratio, 0.61; P=0.02).

Secondary outcomes

Initially, there were significant differences between the plasma (n=230) and standard-care groups (n=271) when it came to:

• Mortality at 24 hours—13.9% and 22.1%, respectively (P=0.02)
• In-hospital mortality—22.2% and 32.5%, respectively (P=0.01)
• Median volume of blood components transfused in the first 24 hours—3 and 4 units, respectively (P=0.02)
• Median volume of red cells transfused in the first 24 hours—3 and 4 units, respectively (P=0.03).
• Median prothrombin-time ratio at first blood sampling—1.2 and 1.3, respectively (P<0.001).

When the researchers adjusted P values for multiple comparisons, the between-group difference in prothrombin-time ratio remained significant (P<0.001).

However, the differences in 24-hour mortality (P=0.55), in-hospital mortality (P=0.33), blood components transfused (P=0.41), and red cells transfused (P=0.69) did not retain significance.

Likewise, there were no significant between-group differences (in adjusted or unadjusted analyses) when it came to multi-organ failure, acute lung injury/acute respiratory distress syndrome, nosocomial infections, or allergic/transfusion-related reactions.

There were 10 adverse events (AEs) considered related to the trial regimen. In the standard-care group, the 4 AEs were sepsis (a serious AE), adult respiratory distress syndrome (a serious AE), fever, and pain.

In the plasma group, the 6 AEs were 2 allergic reactions, 1 case of anaphylaxis, 1 case of hypotension, 1 case of urticaria, and 1 transfusion-related reaction (a serious AE).

Photo by Cristina Granados

Receiving a plasma transfusion during emergency air transport can improve survival for trauma patients, according to a study published in NEJM.

Trauma patients with severe bleeding had a significant decrease in 30-day mortality when they received a plasma transfusion while being airlifted to a hospital.

Transfusion-related reactions and allergic reactions were more common among plasma recipients than patients who only received standard care.

However, this difference was not significant, and most of these reactions were considered minor.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” said study author Jason Sperry, MD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

Patients and intervention

This trial, known as PAMPer (Prehospital Air Medical Plasma), was a phase 3, randomized study enrolling 501 trauma patients at risk of hemorrhagic shock.

Most patients were male (72.7%), and most had suffered blunt trauma (82.4%). About half of patients (51.1%) had prehospital intubation, and more than a third (34.7%) received a prehospital transfusion of red blood cells.

Air medical bases participating in this study were randomized to administer plasma or standard care to eligible patients for 1-month intervals. When the air transport teams were in their plasma interval, they’d begin administering 2 units of thawed plasma to a patient as soon as trial eligibility was confirmed.

If the 2 units were completed during the flight, the team would revert to standard care. If the transfusions weren’t completed, the plasma would continue to be administered when the patient arrived at the trauma center.

The teams administered the assigned treatment 99% of the time (496/501).

In the plasma group, there were 205 patients (89.1%) who received 2 units of plasma, 21 (9.1%) who received 1 unit, and 4 patients (1.7%) who did not receive plasma due to logistical challenges.

In 84.4% of the patients, the plasma infusion was completed during air transport. The remaining patients completed their plasma transfusions at the trauma center.

There was 1 patient (0.4%) in the standard-care group who received plasma before transport began.

Primary outcome

The study’s primary outcome was 30-day mortality. Ninety-six percent of patients (n=481) had data for this outcome—220 patients in the plasma group and 261 in the standard-care group.

Thirty-day mortality was significantly lower in the plasma group than the standard-care group—23.2% and 33.0%, respectively (P=0.03).

In an adjusted analysis, the administration of prehospital plasma was associated with a 39% lower risk for 30-day mortality than standard care (adjusted odds ratio, 0.61; P=0.02).

Secondary outcomes

Initially, there were significant differences between the plasma (n=230) and standard-care groups (n=271) when it came to:

• Mortality at 24 hours—13.9% and 22.1%, respectively (P=0.02)
• In-hospital mortality—22.2% and 32.5%, respectively (P=0.01)
• Median volume of blood components transfused in the first 24 hours—3 and 4 units, respectively (P=0.02)
• Median volume of red cells transfused in the first 24 hours—3 and 4 units, respectively (P=0.03).
• Median prothrombin-time ratio at first blood sampling—1.2 and 1.3, respectively (P<0.001).

When the researchers adjusted P values for multiple comparisons, the between-group difference in prothrombin-time ratio remained significant (P<0.001).

However, the differences in 24-hour mortality (P=0.55), in-hospital mortality (P=0.33), blood components transfused (P=0.41), and red cells transfused (P=0.69) did not retain significance.

Likewise, there were no significant between-group differences (in adjusted or unadjusted analyses) when it came to multi-organ failure, acute lung injury/acute respiratory distress syndrome, nosocomial infections, or allergic/transfusion-related reactions.

There were 10 adverse events (AEs) considered related to the trial regimen. In the standard-care group, the 4 AEs were sepsis (a serious AE), adult respiratory distress syndrome (a serious AE), fever, and pain.

In the plasma group, the 6 AEs were 2 allergic reactions, 1 case of anaphylaxis, 1 case of hypotension, 1 case of urticaria, and 1 transfusion-related reaction (a serious AE).

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

The FP recognized that this patient had multiple dysplastic nevi (DN) and was concerned about a possible melanoma.

Although this patient did not have the familial atypical mole and melanoma (FAMM) syndrome, she was at higher risk of developing a melanoma based on the numerous DN that were so visibly apparent on her trunk. (A diagnosis of FAMM requires the occurrence of melanoma in one or more first- or second-degree relatives.)

Total body photography is the current state-of-the-art technology for monitoring patients with multiple atypical moles at higher risk for skin cancer. Small changes in DN and new nevi can be seen best with this technology. Individual flat lesions also can be monitored with dermoscopy over 3 to 4 months.

It is not recommended, however, to follow a suspicious raised lesion over time with dermoscopy and/or photography because a raised lesion might be a nodular melanoma and a delay of diagnosis of over 3 months may worsen the prognosis. 

In this case, the patient was happy to be referred to a dermatologist with total body photography. Fortunately, the patient reported back to her FP that the dermatologist did not detect any melanomas, and 2 biopsies that were performed came back as DN only.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized that this patient had multiple dysplastic nevi (DN) and was concerned about a possible melanoma.

Although this patient did not have the familial atypical mole and melanoma (FAMM) syndrome, she was at higher risk of developing a melanoma based on the numerous DN that were so visibly apparent on her trunk. (A diagnosis of FAMM requires the occurrence of melanoma in one or more first- or second-degree relatives.)

Total body photography is the current state-of-the-art technology for monitoring patients with multiple atypical moles at higher risk for skin cancer. Small changes in DN and new nevi can be seen best with this technology. Individual flat lesions also can be monitored with dermoscopy over 3 to 4 months.

It is not recommended, however, to follow a suspicious raised lesion over time with dermoscopy and/or photography because a raised lesion might be a nodular melanoma and a delay of diagnosis of over 3 months may worsen the prognosis. 

In this case, the patient was happy to be referred to a dermatologist with total body photography. Fortunately, the patient reported back to her FP that the dermatologist did not detect any melanomas, and 2 biopsies that were performed came back as DN only.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized that this patient had multiple dysplastic nevi (DN) and was concerned about a possible melanoma.

Although this patient did not have the familial atypical mole and melanoma (FAMM) syndrome, she was at higher risk of developing a melanoma based on the numerous DN that were so visibly apparent on her trunk. (A diagnosis of FAMM requires the occurrence of melanoma in one or more first- or second-degree relatives.)

Total body photography is the current state-of-the-art technology for monitoring patients with multiple atypical moles at higher risk for skin cancer. Small changes in DN and new nevi can be seen best with this technology. Individual flat lesions also can be monitored with dermoscopy over 3 to 4 months.

It is not recommended, however, to follow a suspicious raised lesion over time with dermoscopy and/or photography because a raised lesion might be a nodular melanoma and a delay of diagnosis of over 3 months may worsen the prognosis. 

In this case, the patient was happy to be referred to a dermatologist with total body photography. Fortunately, the patient reported back to her FP that the dermatologist did not detect any melanomas, and 2 biopsies that were performed came back as DN only.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]