Helen Heslop, MD

Photo courtesy of Baylor

College of Medicine

NEW YORK—Researchers are creating virus-specific T cells (VST) to treat and prevent viral infections in patients who undergo hematopoietic stem cell transplant.

Thus far, the group has modified T cells with 5 viral vectors—Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and human herpesvirus 6 (HHV6)—and are devising methods whereby these VSTs can be made readily available, off-the-shelf products.

Helen Heslop, MD, of Baylor College of Medicine in Houston, Texas, described the efforts of the Baylor research team at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The team’s tri-virus and 5-virus VST approaches have been described previously. Here, we focus on the team’s efforts to create an off-the-shelf product.

A companion story describes the team’s VST approach to treating type 2 EBV-associated lymphomas.

Despite promising results with these earlier methodologies both as prophylaxis and treatment after stem cell transplant, problems existed with the approaches that would impede broader implementation of VSTs.

“Most of these initial methodologies were complex,” Dr Heslop said.

And even though the production time of the 5-virus VSTs is only 10 days, it does not allow for urgent use.

To solve this problem, the researchers are developing VSTs as off-the-shelf, third-party banked cells for patients who don’t have the time to wait for donor-specific cells to be made.

“The strategy here is that we make lines that are well-characterized but are HLA-restricted and tied to specific viruses,” Dr Heslop said.

The cells are then cryopreserved so that they’re available, and patients receive VSTs according to their HLA type and the line that has suitable activity for their infections.

“We initially evaluated this approach through a multicenter study sponsored by the NHLBI [National Heart, Lung, and Blood Institute],” Dr Heslop said.

Tri-virus approach

The researchers used the original tri-virus methodology, which was lengthy, “but, in this case, because the cells were already available, the time was not a major issue,” Dr Heslop said.

The team also made some new lines for donors with common alleles. In all, they had 32 lines available while the study was running.

They treated 50 patients: 23 received VSTs for CMV, 18 for ADV, and 9 for EBV.

One patient who had CMV colitis received the VSTs and had a complete response (CR), as evidenced by a normal endoscopy with no viral inclusions.

Another patient had EBV persistent after 6 doses of rituximab. One month after receiving the VST infusion, the patient had a CR, even though the cell line had only 1 class 2 allele. And the patient has sustained the CR for several years.

The overall response rate for the study is 74.0% at day 42 after infusion.

The response rate was not significantly different for each virus, Dr Heslop pointed out. Patients with CMV had a 73.9% response rate, those with EBV had a 66.7% response rate, and those with ADV had a 77.8% response rate.

“This is a little bit lower than with the donor-specific T cells, but I think it’s still a promising approach,” she added.

5-virus peptide mix

The researchers are now evaluating the more rapid, 5-virus peptide mix method for creating off-the-shelf VSTs.

This method replaced live viruses with overlapping peptide pools and added immunogenic antigens for 5 viruses, including BKV and HHV6. The process takes only 10 days to produce VSTs.

The team has identified a line for over 90% of the patients screened.

“That’s because we will accept a line that’s only matched at 1 HLA allele, as long as we have activity against the infecting virus through the shared allele,” Dr Heslop explained.

So they’re conducting a clinical trial using this method, and thus far, they have enrolled 22 patients. Sixteen patients have had 1 infusion, and 6 patients have had multiple infusions.

The 22 patients had 25 infections: 10 CMV, 10 BKV, 2 EBV, 2 ADV, and 1 HHV6.

The overall response rate is 88%. Nine of 10 responses in patients with BKV were partial because BK is difficult to clear from urine. However, the BK patients who had hemorrhagic cystitis all had symptomatic improvement.

Dr Heslop pointed out that these results are similar to those at other centers using EBV third-party T cells.

The initial third-party studies were done in Scotland and had a response rate of about 60%, which increased to around 80% in follow-up studies, where they characterized the T cells more extensively.

Both donor-specific and third-party VSTs have low toxicity, sustained response rates, and activity confirmed by studies in multiple centers.

Dr Heslop believes the rapid manufacturing methodologies will facilitate definitive clinical trials.

She said Cell Medica provided support for some of the trials with EBV tumors.

Helen Heslop, MD

Photo courtesy of Baylor

College of Medicine

NEW YORK—Researchers are creating virus-specific T cells (VST) to treat and prevent viral infections in patients who undergo hematopoietic stem cell transplant.

Thus far, the group has modified T cells with 5 viral vectors—Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and human herpesvirus 6 (HHV6)—and are devising methods whereby these VSTs can be made readily available, off-the-shelf products.

Helen Heslop, MD, of Baylor College of Medicine in Houston, Texas, described the efforts of the Baylor research team at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The team’s tri-virus and 5-virus VST approaches have been described previously. Here, we focus on the team’s efforts to create an off-the-shelf product.

A companion story describes the team’s VST approach to treating type 2 EBV-associated lymphomas.

Despite promising results with these earlier methodologies both as prophylaxis and treatment after stem cell transplant, problems existed with the approaches that would impede broader implementation of VSTs.

“Most of these initial methodologies were complex,” Dr Heslop said.

And even though the production time of the 5-virus VSTs is only 10 days, it does not allow for urgent use.

To solve this problem, the researchers are developing VSTs as off-the-shelf, third-party banked cells for patients who don’t have the time to wait for donor-specific cells to be made.

“The strategy here is that we make lines that are well-characterized but are HLA-restricted and tied to specific viruses,” Dr Heslop said.

The cells are then cryopreserved so that they’re available, and patients receive VSTs according to their HLA type and the line that has suitable activity for their infections.

“We initially evaluated this approach through a multicenter study sponsored by the NHLBI [National Heart, Lung, and Blood Institute],” Dr Heslop said.

Tri-virus approach

The researchers used the original tri-virus methodology, which was lengthy, “but, in this case, because the cells were already available, the time was not a major issue,” Dr Heslop said.

The team also made some new lines for donors with common alleles. In all, they had 32 lines available while the study was running.

They treated 50 patients: 23 received VSTs for CMV, 18 for ADV, and 9 for EBV.

One patient who had CMV colitis received the VSTs and had a complete response (CR), as evidenced by a normal endoscopy with no viral inclusions.

Another patient had EBV persistent after 6 doses of rituximab. One month after receiving the VST infusion, the patient had a CR, even though the cell line had only 1 class 2 allele. And the patient has sustained the CR for several years.

The overall response rate for the study is 74.0% at day 42 after infusion.

The response rate was not significantly different for each virus, Dr Heslop pointed out. Patients with CMV had a 73.9% response rate, those with EBV had a 66.7% response rate, and those with ADV had a 77.8% response rate.

“This is a little bit lower than with the donor-specific T cells, but I think it’s still a promising approach,” she added.

5-virus peptide mix

The researchers are now evaluating the more rapid, 5-virus peptide mix method for creating off-the-shelf VSTs.

This method replaced live viruses with overlapping peptide pools and added immunogenic antigens for 5 viruses, including BKV and HHV6. The process takes only 10 days to produce VSTs.

The team has identified a line for over 90% of the patients screened.

“That’s because we will accept a line that’s only matched at 1 HLA allele, as long as we have activity against the infecting virus through the shared allele,” Dr Heslop explained.

So they’re conducting a clinical trial using this method, and thus far, they have enrolled 22 patients. Sixteen patients have had 1 infusion, and 6 patients have had multiple infusions.

The 22 patients had 25 infections: 10 CMV, 10 BKV, 2 EBV, 2 ADV, and 1 HHV6.

The overall response rate is 88%. Nine of 10 responses in patients with BKV were partial because BK is difficult to clear from urine. However, the BK patients who had hemorrhagic cystitis all had symptomatic improvement.

Dr Heslop pointed out that these results are similar to those at other centers using EBV third-party T cells.

The initial third-party studies were done in Scotland and had a response rate of about 60%, which increased to around 80% in follow-up studies, where they characterized the T cells more extensively.

Both donor-specific and third-party VSTs have low toxicity, sustained response rates, and activity confirmed by studies in multiple centers.

Dr Heslop believes the rapid manufacturing methodologies will facilitate definitive clinical trials.

She said Cell Medica provided support for some of the trials with EBV tumors.

Helen Heslop, MD

Photo courtesy of Baylor

College of Medicine

NEW YORK—Researchers are creating virus-specific T cells (VST) to treat and prevent viral infections in patients who undergo hematopoietic stem cell transplant.

Thus far, the group has modified T cells with 5 viral vectors—Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and human herpesvirus 6 (HHV6)—and are devising methods whereby these VSTs can be made readily available, off-the-shelf products.

Helen Heslop, MD, of Baylor College of Medicine in Houston, Texas, described the efforts of the Baylor research team at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The team’s tri-virus and 5-virus VST approaches have been described previously. Here, we focus on the team’s efforts to create an off-the-shelf product.

A companion story describes the team’s VST approach to treating type 2 EBV-associated lymphomas.

Despite promising results with these earlier methodologies both as prophylaxis and treatment after stem cell transplant, problems existed with the approaches that would impede broader implementation of VSTs.

“Most of these initial methodologies were complex,” Dr Heslop said.

And even though the production time of the 5-virus VSTs is only 10 days, it does not allow for urgent use.

To solve this problem, the researchers are developing VSTs as off-the-shelf, third-party banked cells for patients who don’t have the time to wait for donor-specific cells to be made.

“The strategy here is that we make lines that are well-characterized but are HLA-restricted and tied to specific viruses,” Dr Heslop said.

The cells are then cryopreserved so that they’re available, and patients receive VSTs according to their HLA type and the line that has suitable activity for their infections.

“We initially evaluated this approach through a multicenter study sponsored by the NHLBI [National Heart, Lung, and Blood Institute],” Dr Heslop said.

Tri-virus approach

The researchers used the original tri-virus methodology, which was lengthy, “but, in this case, because the cells were already available, the time was not a major issue,” Dr Heslop said.

The team also made some new lines for donors with common alleles. In all, they had 32 lines available while the study was running.

They treated 50 patients: 23 received VSTs for CMV, 18 for ADV, and 9 for EBV.

One patient who had CMV colitis received the VSTs and had a complete response (CR), as evidenced by a normal endoscopy with no viral inclusions.

Another patient had EBV persistent after 6 doses of rituximab. One month after receiving the VST infusion, the patient had a CR, even though the cell line had only 1 class 2 allele. And the patient has sustained the CR for several years.

The overall response rate for the study is 74.0% at day 42 after infusion.

The response rate was not significantly different for each virus, Dr Heslop pointed out. Patients with CMV had a 73.9% response rate, those with EBV had a 66.7% response rate, and those with ADV had a 77.8% response rate.

“This is a little bit lower than with the donor-specific T cells, but I think it’s still a promising approach,” she added.

5-virus peptide mix

The researchers are now evaluating the more rapid, 5-virus peptide mix method for creating off-the-shelf VSTs.

This method replaced live viruses with overlapping peptide pools and added immunogenic antigens for 5 viruses, including BKV and HHV6. The process takes only 10 days to produce VSTs.

The team has identified a line for over 90% of the patients screened.

“That’s because we will accept a line that’s only matched at 1 HLA allele, as long as we have activity against the infecting virus through the shared allele,” Dr Heslop explained.

So they’re conducting a clinical trial using this method, and thus far, they have enrolled 22 patients. Sixteen patients have had 1 infusion, and 6 patients have had multiple infusions.

The 22 patients had 25 infections: 10 CMV, 10 BKV, 2 EBV, 2 ADV, and 1 HHV6.

The overall response rate is 88%. Nine of 10 responses in patients with BKV were partial because BK is difficult to clear from urine. However, the BK patients who had hemorrhagic cystitis all had symptomatic improvement.

Dr Heslop pointed out that these results are similar to those at other centers using EBV third-party T cells.

The initial third-party studies were done in Scotland and had a response rate of about 60%, which increased to around 80% in follow-up studies, where they characterized the T cells more extensively.

Both donor-specific and third-party VSTs have low toxicity, sustained response rates, and activity confirmed by studies in multiple centers.

Dr Heslop believes the rapid manufacturing methodologies will facilitate definitive clinical trials.

She said Cell Medica provided support for some of the trials with EBV tumors.

Warfarin tablets

A new study suggests that certain patients with bioprosthetic aortic heart valves may require anticoagulant therapy.

In some patients, researchers observed reduced motion of the leaflets affecting the valve opening.

The team believes this may be a sign of subclinical leaflet thrombosis, particularly since anticoagulant therapy was able to restore leaflet motion.

The researchers described this study in NEJM.

“Transcatheter and surgically implantable tissue valves are life-saving devices in patients with aortic valve stenosis,” said study author Raj Makkar, MD, of the Cedars-Sinai Heart Institute in Los Angeles, California.

“These findings allow us a potentially valuable opportunity to further optimize the outcomes of these procedures. We are not recommending that all patients with these devices be on blood thinners, but, clearly, further studies need to be done to define best medication regimens.”

Dr Makkar and his colleagues began this research when a clinical trial participant with a bioprosthetic aortic heart valve had a stroke. High-resolution imaging revealed reduced motion of the leaflets that open and close to regulate the flow of blood.

“We wanted to find out if patients undergoing a tissue valve procedure are susceptible to blood clots on the leaflets and study the clinical consequences of the same,” Dr Makkar said.

“We also wanted to understand whether our aortic valve patients were more susceptible to having blood clots and whether those clots could indicate that the patient might experience a neurological complication—a mini-stroke.”

So Dr Makkar and his colleagues analyzed 187 patients who received a new valve via a transcatheter procedure or open-heart surgery—55 patients in a trial and 132 patients enrolled in registries.

All patients underwent high-resolution imaging—4-dimensional CT angiography—so the researchers could detect reduced leaflet motion.

Overall, 20% of patients (39/187) had reduced leaflet motion—40% in the trial (22/55) and 13% (17/132) in the registries. This included patients with multiple bioprosthesis types.

The researchers observed a lower incidence of reduced leaflet motion in patients receiving anticoagulant therapy.

The incidence was significantly lower in patients on warfarin than in those receiving dual antiplatelet therapy. It was 0% and 55%, respectively, in the clinical trial (P=0.01) and 0% and 29%, respectively, in the registry patients (P=0.04).

Dr Makkar and his colleagues also re-evaluated a handful of patients who underwent a follow-up CT—11 who were receiving anticoagulation and 10 who were not. Leaflet motion was restored in all 11 treated patients and 1 of the untreated patients (P<0.001).

Lastly, there was some suggestion that the incidence of stroke or transient ischemic attacks might be higher among patients with reduced valve motion. But the researchers said this finding was inconclusive and requires further study.

Warfarin tablets

A new study suggests that certain patients with bioprosthetic aortic heart valves may require anticoagulant therapy.

In some patients, researchers observed reduced motion of the leaflets affecting the valve opening.

The team believes this may be a sign of subclinical leaflet thrombosis, particularly since anticoagulant therapy was able to restore leaflet motion.

The researchers described this study in NEJM.

“Transcatheter and surgically implantable tissue valves are life-saving devices in patients with aortic valve stenosis,” said study author Raj Makkar, MD, of the Cedars-Sinai Heart Institute in Los Angeles, California.

“These findings allow us a potentially valuable opportunity to further optimize the outcomes of these procedures. We are not recommending that all patients with these devices be on blood thinners, but, clearly, further studies need to be done to define best medication regimens.”

Dr Makkar and his colleagues began this research when a clinical trial participant with a bioprosthetic aortic heart valve had a stroke. High-resolution imaging revealed reduced motion of the leaflets that open and close to regulate the flow of blood.

“We wanted to find out if patients undergoing a tissue valve procedure are susceptible to blood clots on the leaflets and study the clinical consequences of the same,” Dr Makkar said.

“We also wanted to understand whether our aortic valve patients were more susceptible to having blood clots and whether those clots could indicate that the patient might experience a neurological complication—a mini-stroke.”

So Dr Makkar and his colleagues analyzed 187 patients who received a new valve via a transcatheter procedure or open-heart surgery—55 patients in a trial and 132 patients enrolled in registries.

All patients underwent high-resolution imaging—4-dimensional CT angiography—so the researchers could detect reduced leaflet motion.

Overall, 20% of patients (39/187) had reduced leaflet motion—40% in the trial (22/55) and 13% (17/132) in the registries. This included patients with multiple bioprosthesis types.

The researchers observed a lower incidence of reduced leaflet motion in patients receiving anticoagulant therapy.

The incidence was significantly lower in patients on warfarin than in those receiving dual antiplatelet therapy. It was 0% and 55%, respectively, in the clinical trial (P=0.01) and 0% and 29%, respectively, in the registry patients (P=0.04).

Dr Makkar and his colleagues also re-evaluated a handful of patients who underwent a follow-up CT—11 who were receiving anticoagulation and 10 who were not. Leaflet motion was restored in all 11 treated patients and 1 of the untreated patients (P<0.001).

Lastly, there was some suggestion that the incidence of stroke or transient ischemic attacks might be higher among patients with reduced valve motion. But the researchers said this finding was inconclusive and requires further study.

Warfarin tablets

A new study suggests that certain patients with bioprosthetic aortic heart valves may require anticoagulant therapy.

In some patients, researchers observed reduced motion of the leaflets affecting the valve opening.

The team believes this may be a sign of subclinical leaflet thrombosis, particularly since anticoagulant therapy was able to restore leaflet motion.

The researchers described this study in NEJM.

“Transcatheter and surgically implantable tissue valves are life-saving devices in patients with aortic valve stenosis,” said study author Raj Makkar, MD, of the Cedars-Sinai Heart Institute in Los Angeles, California.

“These findings allow us a potentially valuable opportunity to further optimize the outcomes of these procedures. We are not recommending that all patients with these devices be on blood thinners, but, clearly, further studies need to be done to define best medication regimens.”

Dr Makkar and his colleagues began this research when a clinical trial participant with a bioprosthetic aortic heart valve had a stroke. High-resolution imaging revealed reduced motion of the leaflets that open and close to regulate the flow of blood.

“We wanted to find out if patients undergoing a tissue valve procedure are susceptible to blood clots on the leaflets and study the clinical consequences of the same,” Dr Makkar said.

“We also wanted to understand whether our aortic valve patients were more susceptible to having blood clots and whether those clots could indicate that the patient might experience a neurological complication—a mini-stroke.”

So Dr Makkar and his colleagues analyzed 187 patients who received a new valve via a transcatheter procedure or open-heart surgery—55 patients in a trial and 132 patients enrolled in registries.

All patients underwent high-resolution imaging—4-dimensional CT angiography—so the researchers could detect reduced leaflet motion.

Overall, 20% of patients (39/187) had reduced leaflet motion—40% in the trial (22/55) and 13% (17/132) in the registries. This included patients with multiple bioprosthesis types.

The researchers observed a lower incidence of reduced leaflet motion in patients receiving anticoagulant therapy.

The incidence was significantly lower in patients on warfarin than in those receiving dual antiplatelet therapy. It was 0% and 55%, respectively, in the clinical trial (P=0.01) and 0% and 29%, respectively, in the registry patients (P=0.04).

Dr Makkar and his colleagues also re-evaluated a handful of patients who underwent a follow-up CT—11 who were receiving anticoagulation and 10 who were not. Leaflet motion was restored in all 11 treated patients and 1 of the untreated patients (P<0.001).

Lastly, there was some suggestion that the incidence of stroke or transient ischemic attacks might be higher among patients with reduced valve motion. But the researchers said this finding was inconclusive and requires further study.

Youyou Tu

Three researchers have won the 2015 Nobel Prize in Physiology or Medicine for discoveries related to parasitic diseases.

One half of the prize was awarded to Youyou Tu for discoveries concerning a novel therapy against malaria—artemisinin.

The other half of the prize was awarded to William C. Campbell, PhD, and Satoshi Ōmura, PhD, for their discoveries concerning a novel therapy against infections caused by roundworm parasites.

Drs Ōmura and Campbell discovered the drug avermectin. A derivative of this drug has lowered the incidence of river blindness and lymphatic filariasis and demonstrated efficacy against other parasitic diseases.

Artemisinin

Before artemisinin came into use, malaria was treated with chloroquine or quinine—with declining success. By the late 1960s, efforts to eradicate malaria had failed, and the disease was on the rise.

At that time, Tu turned to traditional herbal medicine to tackle the challenge of developing novel malaria therapies. From a large-scale screen of herbal remedies in malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate.

However, the results were inconsistent. So Tu revisited the ancient literature and discovered clues that guided her in her quest to extract the active component from Artemisia annua. Tu was the first to show that this component, later called artemisinin, was effective against the malaria parasite in animals and humans.

Artemisinin is now used in all malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from malaria by more than 20% overall and by more than 30% in children.

Avermectin

The discovery of avermectin began with Streptomyces, bacteria that live in the soil and are known to produce agents with antibacterial activities.

Dr Ōmura isolated new strains of Streptomyces from soil samples and cultured them in the lab. He selected about 50 of the most promising cultures to analyze for their activity against harmful microorganisms. One of these cultures turned out to be Streptomyces avermitilis, the source of avermectin.

Dr Campbell acquired Dr Ōmura’s Streptomyces cultures and explored their efficacy. Dr Campbell showed that a component from one of the cultures could combat parasites in domestic and farm animals.

The bioactive agent was purified and named avermectin. It was subsequently modified to a more effective compound called ivermectin. Ivermectin turned out to be effective against a variety of parasites, including those that cause river blindness and lymphatic filariasis.

Today, ivermectin is used in all parts of the world that are plagued by parasitic diseases. The drug has proven effective against a range of parasites and has limited side effects. Thanks to ivermectin, river blindness and lymphatic filariasis are on the verge of eradication.

About the winners

Youyou Tu was born in 1930 in China. She graduated from Beijing Medical University in 1955. Tu has worked at the China Academy of Traditional Chinese Medicine since 1965. She has been chief professor there since 2000.

William C. Campbell was born in 1930 in Ramelton, Ireland. He received a BA from Trinity College, University of Dublin, in Ireland in 1952. He received a PhD from the University of Wisconsin in Madison, Wisconsin, in 1957.

From 1957 to 1990, Dr Campbell was with the Merck Institute for Therapeutic Research, from 1984 to 1990 as a senior scientist and director for assay research and development. Dr Campbell is currently a research fellow emeritus at Drew University in Madison, New Jersey.

Satoshi Ōmura was born in 1935 in the Yamanashi Prefecture, Japan. He received a PhD in pharmaceutical sciences in 1968 from the University of Tokyo and a PhD in chemistry in 1970 from Tokyo University of Science.

Dr Ōmura was a researcher at the Kitasato Institute in Japan from 1965 to 1971 and a professor at Kitasato University from 1975 to 2007. Since 2007, Dr Ōmura has been a professor emeritus at Kitasato University.

Youyou Tu

Three researchers have won the 2015 Nobel Prize in Physiology or Medicine for discoveries related to parasitic diseases.

One half of the prize was awarded to Youyou Tu for discoveries concerning a novel therapy against malaria—artemisinin.

The other half of the prize was awarded to William C. Campbell, PhD, and Satoshi Ōmura, PhD, for their discoveries concerning a novel therapy against infections caused by roundworm parasites.

Drs Ōmura and Campbell discovered the drug avermectin. A derivative of this drug has lowered the incidence of river blindness and lymphatic filariasis and demonstrated efficacy against other parasitic diseases.

Artemisinin

Before artemisinin came into use, malaria was treated with chloroquine or quinine—with declining success. By the late 1960s, efforts to eradicate malaria had failed, and the disease was on the rise.

At that time, Tu turned to traditional herbal medicine to tackle the challenge of developing novel malaria therapies. From a large-scale screen of herbal remedies in malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate.

However, the results were inconsistent. So Tu revisited the ancient literature and discovered clues that guided her in her quest to extract the active component from Artemisia annua. Tu was the first to show that this component, later called artemisinin, was effective against the malaria parasite in animals and humans.

Artemisinin is now used in all malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from malaria by more than 20% overall and by more than 30% in children.

Avermectin

The discovery of avermectin began with Streptomyces, bacteria that live in the soil and are known to produce agents with antibacterial activities.

Dr Ōmura isolated new strains of Streptomyces from soil samples and cultured them in the lab. He selected about 50 of the most promising cultures to analyze for their activity against harmful microorganisms. One of these cultures turned out to be Streptomyces avermitilis, the source of avermectin.

Dr Campbell acquired Dr Ōmura’s Streptomyces cultures and explored their efficacy. Dr Campbell showed that a component from one of the cultures could combat parasites in domestic and farm animals.

The bioactive agent was purified and named avermectin. It was subsequently modified to a more effective compound called ivermectin. Ivermectin turned out to be effective against a variety of parasites, including those that cause river blindness and lymphatic filariasis.

Today, ivermectin is used in all parts of the world that are plagued by parasitic diseases. The drug has proven effective against a range of parasites and has limited side effects. Thanks to ivermectin, river blindness and lymphatic filariasis are on the verge of eradication.

About the winners

Youyou Tu was born in 1930 in China. She graduated from Beijing Medical University in 1955. Tu has worked at the China Academy of Traditional Chinese Medicine since 1965. She has been chief professor there since 2000.

William C. Campbell was born in 1930 in Ramelton, Ireland. He received a BA from Trinity College, University of Dublin, in Ireland in 1952. He received a PhD from the University of Wisconsin in Madison, Wisconsin, in 1957.

From 1957 to 1990, Dr Campbell was with the Merck Institute for Therapeutic Research, from 1984 to 1990 as a senior scientist and director for assay research and development. Dr Campbell is currently a research fellow emeritus at Drew University in Madison, New Jersey.

Satoshi Ōmura was born in 1935 in the Yamanashi Prefecture, Japan. He received a PhD in pharmaceutical sciences in 1968 from the University of Tokyo and a PhD in chemistry in 1970 from Tokyo University of Science.

Dr Ōmura was a researcher at the Kitasato Institute in Japan from 1965 to 1971 and a professor at Kitasato University from 1975 to 2007. Since 2007, Dr Ōmura has been a professor emeritus at Kitasato University.

Youyou Tu

Three researchers have won the 2015 Nobel Prize in Physiology or Medicine for discoveries related to parasitic diseases.

One half of the prize was awarded to Youyou Tu for discoveries concerning a novel therapy against malaria—artemisinin.

The other half of the prize was awarded to William C. Campbell, PhD, and Satoshi Ōmura, PhD, for their discoveries concerning a novel therapy against infections caused by roundworm parasites.

Drs Ōmura and Campbell discovered the drug avermectin. A derivative of this drug has lowered the incidence of river blindness and lymphatic filariasis and demonstrated efficacy against other parasitic diseases.

Artemisinin

Before artemisinin came into use, malaria was treated with chloroquine or quinine—with declining success. By the late 1960s, efforts to eradicate malaria had failed, and the disease was on the rise.

At that time, Tu turned to traditional herbal medicine to tackle the challenge of developing novel malaria therapies. From a large-scale screen of herbal remedies in malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate.

However, the results were inconsistent. So Tu revisited the ancient literature and discovered clues that guided her in her quest to extract the active component from Artemisia annua. Tu was the first to show that this component, later called artemisinin, was effective against the malaria parasite in animals and humans.

Artemisinin is now used in all malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from malaria by more than 20% overall and by more than 30% in children.

Avermectin

The discovery of avermectin began with Streptomyces, bacteria that live in the soil and are known to produce agents with antibacterial activities.

Dr Ōmura isolated new strains of Streptomyces from soil samples and cultured them in the lab. He selected about 50 of the most promising cultures to analyze for their activity against harmful microorganisms. One of these cultures turned out to be Streptomyces avermitilis, the source of avermectin.

Dr Campbell acquired Dr Ōmura’s Streptomyces cultures and explored their efficacy. Dr Campbell showed that a component from one of the cultures could combat parasites in domestic and farm animals.

The bioactive agent was purified and named avermectin. It was subsequently modified to a more effective compound called ivermectin. Ivermectin turned out to be effective against a variety of parasites, including those that cause river blindness and lymphatic filariasis.

Today, ivermectin is used in all parts of the world that are plagued by parasitic diseases. The drug has proven effective against a range of parasites and has limited side effects. Thanks to ivermectin, river blindness and lymphatic filariasis are on the verge of eradication.

About the winners

Youyou Tu was born in 1930 in China. She graduated from Beijing Medical University in 1955. Tu has worked at the China Academy of Traditional Chinese Medicine since 1965. She has been chief professor there since 2000.

William C. Campbell was born in 1930 in Ramelton, Ireland. He received a BA from Trinity College, University of Dublin, in Ireland in 1952. He received a PhD from the University of Wisconsin in Madison, Wisconsin, in 1957.

From 1957 to 1990, Dr Campbell was with the Merck Institute for Therapeutic Research, from 1984 to 1990 as a senior scientist and director for assay research and development. Dr Campbell is currently a research fellow emeritus at Drew University in Madison, New Jersey.

Satoshi Ōmura was born in 1935 in the Yamanashi Prefecture, Japan. He received a PhD in pharmaceutical sciences in 1968 from the University of Tokyo and a PhD in chemistry in 1970 from Tokyo University of Science.

Dr Ōmura was a researcher at the Kitasato Institute in Japan from 1965 to 1971 and a professor at Kitasato University from 1975 to 2007. Since 2007, Dr Ōmura has been a professor emeritus at Kitasato University.

Left ventricular assist devices (LVADs) are rapidly becoming commonplace treatment for end-stage heart failure, either as a bridge to transplant or as destination therapy alone.^1,2 More and more patients are surviving with LVAD therapy and going on to live longer, fuller lives. As a result, unfortunately, more LVAD patients are being admitted and readmitted to the hospital for common non-cardiac illnesses.

For five years, Bon Secours St. Mary’s Hospital in Richmond, Va., has been one of the few community hospitals with an advanced heart failure and LVAD program. Historically, when LVAD patients presented for admission with noncardiac complaints, they were deemed too complex for general care and admitted by their cardiothoracic surgeon or cardiologist. Over a year ago, the hospitalist group at St. Mary’s met with leadership of our advance heart failure program to try to improve and streamline care for these patients. This conversation spawned our LVAD medical management program.

At the outset, more than 80% of our hospitalists had hands-on experience with LVAD management. Although there was a good base of understanding of cardiac functioning and the physiology of mechanical assistance, the nuances of such subspecialized care created a great deal of anxiety. To create a knowledge base to build up, we developed a training curriculum that included online didactics and hands-on training with an LVAD. All hospitalists at St. Mary’s underwent three hours of training online through the Thoratec provider portal for the HeartMate II left ventricular assist device, and, subsequently, an in-person education session by heart failure coordinators. All new hospitalists complete the same training within six months of their hire date.

As we moved forward with the program, we set clear expectations. Our hospitalists are not expected to manage the LVAD directly; however, knowledge of the device parameters (i.e., rotor speed, power, and pulse index) is necessary for diagnosis and management of patients. The heart failure team is consulted on every LVAD patient who is admitted to the hospital for device management and LVAD-related complications.

A hospitalist attending admitted the first LVAD patient more than a year ago. Patients admitted under the hospitalist service are at least six months post-LVAD implantation. In review, we believe that six months was a conservative starting point. Our hospitalists' confidence and comfort with this population has grown over the year and allowed us to consider taking on these patients much sooner after implantation.

Since initiating the program, we have admitted 15 unique patients for 33 separate encounters. The hospitalist team has provided care for illnesses commonly experienced by LVAD patients, such as GI bleeding and drive-line site infection, as well as general medicine complaints (concussion, septic arthritis, lung cancer, and pneumonia).^3,4

Our team manages more than 90% of the St. Mary's non-surgical adult patients, and in reality, the role we play for these patients is much the same as for other complex medical and surgical patients. We provide first point of contact, diagnosis and treatment, coordination of subspecialty care, and safe discharge.

The program of hospitalist care for LVAD patients at St. Mary’s has passed its first birthday. It’s an innovation that we’re very proud of. Since the outset of our care for these patients, we have been collecting data about patient outcomes, length of stay, and resource utilization. Moving forward, we plan to begin identifying places where we can improve the general medical care for this specialized group of patients. TH

Dr. Thistlethwaite is an adult hospitalist at Bon Secours St. Mary’s Hospital in Richmond, Va. Dr. Mbanu is chief of the adult hospitalist department at St. Mary’s Hospital and medical director of clinical integration at Bon Secours Health System, Inc.

Editor's note: this article was updated Feb. 3, 2016.

References

1. Lampropulos JF, Kim N, Wang Y, et al. Trends in left ventricular assist device use and outcomes among Medicare beneficiaries, 2004–2011. Open Heart. 2014;1(1):e000109. doi:10.1136/openhrt-2014-000109.
2. Jorde UP, Kushwaha SS, Tatooles AJ, et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63(17):1751-1757.
3. Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Card Surg. 2010;25(3):352-356.
4. Fischer SA, Trenholme GM, Costanzo MR, Piccione W. Infectious complications in left ventricular assist device recipients. Clin Infect Dis. 1997;24(1):18-23.

Left ventricular assist devices (LVADs) are rapidly becoming commonplace treatment for end-stage heart failure, either as a bridge to transplant or as destination therapy alone.^1,2 More and more patients are surviving with LVAD therapy and going on to live longer, fuller lives. As a result, unfortunately, more LVAD patients are being admitted and readmitted to the hospital for common non-cardiac illnesses.

For five years, Bon Secours St. Mary’s Hospital in Richmond, Va., has been one of the few community hospitals with an advanced heart failure and LVAD program. Historically, when LVAD patients presented for admission with noncardiac complaints, they were deemed too complex for general care and admitted by their cardiothoracic surgeon or cardiologist. Over a year ago, the hospitalist group at St. Mary’s met with leadership of our advance heart failure program to try to improve and streamline care for these patients. This conversation spawned our LVAD medical management program.

At the outset, more than 80% of our hospitalists had hands-on experience with LVAD management. Although there was a good base of understanding of cardiac functioning and the physiology of mechanical assistance, the nuances of such subspecialized care created a great deal of anxiety. To create a knowledge base to build up, we developed a training curriculum that included online didactics and hands-on training with an LVAD. All hospitalists at St. Mary’s underwent three hours of training online through the Thoratec provider portal for the HeartMate II left ventricular assist device, and, subsequently, an in-person education session by heart failure coordinators. All new hospitalists complete the same training within six months of their hire date.

As we moved forward with the program, we set clear expectations. Our hospitalists are not expected to manage the LVAD directly; however, knowledge of the device parameters (i.e., rotor speed, power, and pulse index) is necessary for diagnosis and management of patients. The heart failure team is consulted on every LVAD patient who is admitted to the hospital for device management and LVAD-related complications.

A hospitalist attending admitted the first LVAD patient more than a year ago. Patients admitted under the hospitalist service are at least six months post-LVAD implantation. In review, we believe that six months was a conservative starting point. Our hospitalists' confidence and comfort with this population has grown over the year and allowed us to consider taking on these patients much sooner after implantation.

Since initiating the program, we have admitted 15 unique patients for 33 separate encounters. The hospitalist team has provided care for illnesses commonly experienced by LVAD patients, such as GI bleeding and drive-line site infection, as well as general medicine complaints (concussion, septic arthritis, lung cancer, and pneumonia).^3,4

Our team manages more than 90% of the St. Mary's non-surgical adult patients, and in reality, the role we play for these patients is much the same as for other complex medical and surgical patients. We provide first point of contact, diagnosis and treatment, coordination of subspecialty care, and safe discharge.

The program of hospitalist care for LVAD patients at St. Mary’s has passed its first birthday. It’s an innovation that we’re very proud of. Since the outset of our care for these patients, we have been collecting data about patient outcomes, length of stay, and resource utilization. Moving forward, we plan to begin identifying places where we can improve the general medical care for this specialized group of patients. TH

Dr. Thistlethwaite is an adult hospitalist at Bon Secours St. Mary’s Hospital in Richmond, Va. Dr. Mbanu is chief of the adult hospitalist department at St. Mary’s Hospital and medical director of clinical integration at Bon Secours Health System, Inc.

Editor's note: this article was updated Feb. 3, 2016.

References

1. Lampropulos JF, Kim N, Wang Y, et al. Trends in left ventricular assist device use and outcomes among Medicare beneficiaries, 2004–2011. Open Heart. 2014;1(1):e000109. doi:10.1136/openhrt-2014-000109.
2. Jorde UP, Kushwaha SS, Tatooles AJ, et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63(17):1751-1757.
3. Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Card Surg. 2010;25(3):352-356.
4. Fischer SA, Trenholme GM, Costanzo MR, Piccione W. Infectious complications in left ventricular assist device recipients. Clin Infect Dis. 1997;24(1):18-23.

Left ventricular assist devices (LVADs) are rapidly becoming commonplace treatment for end-stage heart failure, either as a bridge to transplant or as destination therapy alone.^1,2 More and more patients are surviving with LVAD therapy and going on to live longer, fuller lives. As a result, unfortunately, more LVAD patients are being admitted and readmitted to the hospital for common non-cardiac illnesses.

For five years, Bon Secours St. Mary’s Hospital in Richmond, Va., has been one of the few community hospitals with an advanced heart failure and LVAD program. Historically, when LVAD patients presented for admission with noncardiac complaints, they were deemed too complex for general care and admitted by their cardiothoracic surgeon or cardiologist. Over a year ago, the hospitalist group at St. Mary’s met with leadership of our advance heart failure program to try to improve and streamline care for these patients. This conversation spawned our LVAD medical management program.

At the outset, more than 80% of our hospitalists had hands-on experience with LVAD management. Although there was a good base of understanding of cardiac functioning and the physiology of mechanical assistance, the nuances of such subspecialized care created a great deal of anxiety. To create a knowledge base to build up, we developed a training curriculum that included online didactics and hands-on training with an LVAD. All hospitalists at St. Mary’s underwent three hours of training online through the Thoratec provider portal for the HeartMate II left ventricular assist device, and, subsequently, an in-person education session by heart failure coordinators. All new hospitalists complete the same training within six months of their hire date.

As we moved forward with the program, we set clear expectations. Our hospitalists are not expected to manage the LVAD directly; however, knowledge of the device parameters (i.e., rotor speed, power, and pulse index) is necessary for diagnosis and management of patients. The heart failure team is consulted on every LVAD patient who is admitted to the hospital for device management and LVAD-related complications.

A hospitalist attending admitted the first LVAD patient more than a year ago. Patients admitted under the hospitalist service are at least six months post-LVAD implantation. In review, we believe that six months was a conservative starting point. Our hospitalists' confidence and comfort with this population has grown over the year and allowed us to consider taking on these patients much sooner after implantation.

Since initiating the program, we have admitted 15 unique patients for 33 separate encounters. The hospitalist team has provided care for illnesses commonly experienced by LVAD patients, such as GI bleeding and drive-line site infection, as well as general medicine complaints (concussion, septic arthritis, lung cancer, and pneumonia).^3,4

Our team manages more than 90% of the St. Mary's non-surgical adult patients, and in reality, the role we play for these patients is much the same as for other complex medical and surgical patients. We provide first point of contact, diagnosis and treatment, coordination of subspecialty care, and safe discharge.

The program of hospitalist care for LVAD patients at St. Mary’s has passed its first birthday. It’s an innovation that we’re very proud of. Since the outset of our care for these patients, we have been collecting data about patient outcomes, length of stay, and resource utilization. Moving forward, we plan to begin identifying places where we can improve the general medical care for this specialized group of patients. TH

Dr. Thistlethwaite is an adult hospitalist at Bon Secours St. Mary’s Hospital in Richmond, Va. Dr. Mbanu is chief of the adult hospitalist department at St. Mary’s Hospital and medical director of clinical integration at Bon Secours Health System, Inc.

Editor's note: this article was updated Feb. 3, 2016.

References

1. Lampropulos JF, Kim N, Wang Y, et al. Trends in left ventricular assist device use and outcomes among Medicare beneficiaries, 2004–2011. Open Heart. 2014;1(1):e000109. doi:10.1136/openhrt-2014-000109.
2. Jorde UP, Kushwaha SS, Tatooles AJ, et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63(17):1751-1757.
3. Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Card Surg. 2010;25(3):352-356.
4. Fischer SA, Trenholme GM, Costanzo MR, Piccione W. Infectious complications in left ventricular assist device recipients. Clin Infect Dis. 1997;24(1):18-23.

Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?

Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.

Study design: Multi-center, randomized, noninferiority trial.

Setting: Six ICUs in France.

Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.

Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.

There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.

Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.

Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.

Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?

Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.

Study design: Multi-center, randomized, noninferiority trial.

Setting: Six ICUs in France.

Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.

Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.

There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.

Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.

Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.

Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?

Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.

Study design: Multi-center, randomized, noninferiority trial.

Setting: Six ICUs in France.

Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.

Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.

There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.

Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.

Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.

Clinical question: Does routine oxygen supplementation in patients with STEMI increase myocardial injury?

Background: Because of physiologic and clinical studies conducted before the era of acute coronary intervention, supplemental oxygen routinely is administered to patients with STEMI, regardless of oxygen saturation; however, recent studies have shown possible adverse effects of oxygen, including increased reperfusion injury and increased adverse outcomes in small clinical trials.

Study design: Multicenter, prospective, randomized, controlled trial (RCT).

Setting: Nine metropolitan hospitals.

Synopsis: This multicenter study included 441 patients with STEMI who were 18 years or older and were randomized by paramedics to receive either 8 L/min of oxygen or no supplemental oxygen. All patients then received protocolized care. The primary endpoint of myocardial infarct size, determined by mean peak of creatine kinase, was significantly increased in the oxygen group compared to the no oxygen group (1948 vs. 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There were nonsignificant increases of secondary endpoints in the oxygen group, including rate of recurrent myocardial infarction (5.5% vs. 0.9%; P=0.006), frequency of arrhythmia (40.4% vs. 31.4%; P=0.05), and size of infarct on six-month cardiac MRI (n=139; 20.3 vs. 13.1 g; P=0.04).

This study has several limitations: It was powered to detect differences in biomarkers (not clinical endpoints) and the treatment was not blinded to paramedics, patients, or cardiology teams.

Bottom line: Supplemental oxygen administration in patients with STEMI might increase infarct size and lead to poorer clinical outcomes; however, larger clinical trials are warranted.

Citation: Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation. 2015;131(24):2143-2150.

Clinical question: Does routine oxygen supplementation in patients with STEMI increase myocardial injury?

Background: Because of physiologic and clinical studies conducted before the era of acute coronary intervention, supplemental oxygen routinely is administered to patients with STEMI, regardless of oxygen saturation; however, recent studies have shown possible adverse effects of oxygen, including increased reperfusion injury and increased adverse outcomes in small clinical trials.

Study design: Multicenter, prospective, randomized, controlled trial (RCT).

Setting: Nine metropolitan hospitals.

Synopsis: This multicenter study included 441 patients with STEMI who were 18 years or older and were randomized by paramedics to receive either 8 L/min of oxygen or no supplemental oxygen. All patients then received protocolized care. The primary endpoint of myocardial infarct size, determined by mean peak of creatine kinase, was significantly increased in the oxygen group compared to the no oxygen group (1948 vs. 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There were nonsignificant increases of secondary endpoints in the oxygen group, including rate of recurrent myocardial infarction (5.5% vs. 0.9%; P=0.006), frequency of arrhythmia (40.4% vs. 31.4%; P=0.05), and size of infarct on six-month cardiac MRI (n=139; 20.3 vs. 13.1 g; P=0.04).

This study has several limitations: It was powered to detect differences in biomarkers (not clinical endpoints) and the treatment was not blinded to paramedics, patients, or cardiology teams.

Bottom line: Supplemental oxygen administration in patients with STEMI might increase infarct size and lead to poorer clinical outcomes; however, larger clinical trials are warranted.

Citation: Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation. 2015;131(24):2143-2150.

Clinical question: Does routine oxygen supplementation in patients with STEMI increase myocardial injury?

Background: Because of physiologic and clinical studies conducted before the era of acute coronary intervention, supplemental oxygen routinely is administered to patients with STEMI, regardless of oxygen saturation; however, recent studies have shown possible adverse effects of oxygen, including increased reperfusion injury and increased adverse outcomes in small clinical trials.

Study design: Multicenter, prospective, randomized, controlled trial (RCT).

Setting: Nine metropolitan hospitals.

Synopsis: This multicenter study included 441 patients with STEMI who were 18 years or older and were randomized by paramedics to receive either 8 L/min of oxygen or no supplemental oxygen. All patients then received protocolized care. The primary endpoint of myocardial infarct size, determined by mean peak of creatine kinase, was significantly increased in the oxygen group compared to the no oxygen group (1948 vs. 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There were nonsignificant increases of secondary endpoints in the oxygen group, including rate of recurrent myocardial infarction (5.5% vs. 0.9%; P=0.006), frequency of arrhythmia (40.4% vs. 31.4%; P=0.05), and size of infarct on six-month cardiac MRI (n=139; 20.3 vs. 13.1 g; P=0.04).

This study has several limitations: It was powered to detect differences in biomarkers (not clinical endpoints) and the treatment was not blinded to paramedics, patients, or cardiology teams.

Bottom line: Supplemental oxygen administration in patients with STEMI might increase infarct size and lead to poorer clinical outcomes; however, larger clinical trials are warranted.

Citation: Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation. 2015;131(24):2143-2150.

Clinical question: Does thrombectomy, in conjunction with medical therapy, improve functional independence in patients with an acute proximal anterior stroke?

Background: Revascularization of proximal anterior strokes with alteplase alone occurs less than 50% of the time. First-generation thrombectomy devices (i.e., Merci and Penumbra) have not shown improvement in revascularization or functional outcomes; however, the development of thrombectomy stent retriever devices has led to more promising results, with several recent studies demonstrating functional improvement using endovascular retrieval in addition to medical therapy in proximal anterior circulation strokes.

Study design: Prospective, multicenter, randomized, sequential, open-label, phase 3 study with blinded evaluation.

Setting: Four hospitals in Spain.

Synopsis: Approximately 200 patients who were diagnosed within eight hours of onset of a large vessel anterior stroke were randomly assigned to medical therapy (alteplase) plus endovascular treatment versus medical therapy alone. In order to reduce selection bias, the study was conducted within a population-based registry of acute stroke patients from the same area. The major exclusion criterion was evidence of a large infarct on imaging. The primary outcome was severity of disability at 90 days based on the modified Rankin score.

Study results showed a significant improvement in functional status in the thrombectomy group, with 66% of patients demonstrating revascularization. The rate of death and intracranial hemorrhage was similar between both groups.

The trial stopped recruitment after the first interim analysis given lack of equipoise, with emerging literature supporting endovascular therapy.

Bottom line: Thrombectomy performed in proximal, large vessel anterior circulation strokes within eight hours of onset of symptoms improves functional status at 90 days.

Citation: Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptoms onset in ischemic stroke. New Engl J Med. 2015;372(24):2296-2306.

Clinical question: Does thrombectomy, in conjunction with medical therapy, improve functional independence in patients with an acute proximal anterior stroke?

Background: Revascularization of proximal anterior strokes with alteplase alone occurs less than 50% of the time. First-generation thrombectomy devices (i.e., Merci and Penumbra) have not shown improvement in revascularization or functional outcomes; however, the development of thrombectomy stent retriever devices has led to more promising results, with several recent studies demonstrating functional improvement using endovascular retrieval in addition to medical therapy in proximal anterior circulation strokes.

Study design: Prospective, multicenter, randomized, sequential, open-label, phase 3 study with blinded evaluation.

Setting: Four hospitals in Spain.

Synopsis: Approximately 200 patients who were diagnosed within eight hours of onset of a large vessel anterior stroke were randomly assigned to medical therapy (alteplase) plus endovascular treatment versus medical therapy alone. In order to reduce selection bias, the study was conducted within a population-based registry of acute stroke patients from the same area. The major exclusion criterion was evidence of a large infarct on imaging. The primary outcome was severity of disability at 90 days based on the modified Rankin score.

Study results showed a significant improvement in functional status in the thrombectomy group, with 66% of patients demonstrating revascularization. The rate of death and intracranial hemorrhage was similar between both groups.

The trial stopped recruitment after the first interim analysis given lack of equipoise, with emerging literature supporting endovascular therapy.

Bottom line: Thrombectomy performed in proximal, large vessel anterior circulation strokes within eight hours of onset of symptoms improves functional status at 90 days.

Citation: Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptoms onset in ischemic stroke. New Engl J Med. 2015;372(24):2296-2306.

Clinical question: Does thrombectomy, in conjunction with medical therapy, improve functional independence in patients with an acute proximal anterior stroke?

Background: Revascularization of proximal anterior strokes with alteplase alone occurs less than 50% of the time. First-generation thrombectomy devices (i.e., Merci and Penumbra) have not shown improvement in revascularization or functional outcomes; however, the development of thrombectomy stent retriever devices has led to more promising results, with several recent studies demonstrating functional improvement using endovascular retrieval in addition to medical therapy in proximal anterior circulation strokes.

Study design: Prospective, multicenter, randomized, sequential, open-label, phase 3 study with blinded evaluation.

Setting: Four hospitals in Spain.

Synopsis: Approximately 200 patients who were diagnosed within eight hours of onset of a large vessel anterior stroke were randomly assigned to medical therapy (alteplase) plus endovascular treatment versus medical therapy alone. In order to reduce selection bias, the study was conducted within a population-based registry of acute stroke patients from the same area. The major exclusion criterion was evidence of a large infarct on imaging. The primary outcome was severity of disability at 90 days based on the modified Rankin score.

Study results showed a significant improvement in functional status in the thrombectomy group, with 66% of patients demonstrating revascularization. The rate of death and intracranial hemorrhage was similar between both groups.

The trial stopped recruitment after the first interim analysis given lack of equipoise, with emerging literature supporting endovascular therapy.

Bottom line: Thrombectomy performed in proximal, large vessel anterior circulation strokes within eight hours of onset of symptoms improves functional status at 90 days.

Citation: Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptoms onset in ischemic stroke. New Engl J Med. 2015;372(24):2296-2306.

Clinical question: Does interdisciplinary care on general medical wards improve patient outcomes?

Background: Patients on general medical wards might experience errors and/or preventable deaths. One mechanism that could reduce the risk of errors or preventable death is the utilization of interdisciplinary team care.

Study design: Systematic review.

Setting: Studies published in English from 1998 through 2013 in Embase, MEDLINE, and PsycINFO.

Synopsis: Reports of interdisciplinary team care interventions on general medical wards in which the care was evaluated against an objective patient outcome were reviewed. Outcomes were grouped into early (less than 30 days) or late (30 days to 12 months). Thirty studies of more than 66,000 total patients were included; these were composed of RCTs, nonrandomized cluster trials, and controlled before-after studies.

Interventions either altered the composition of the care team or addressed the logistics of team practice. Studies evaluated complications of care, length of stay, readmissions, and mortality. Although some evidence showed interdisciplinary care reduces complications, the majority of studies did not show significant improvements in any other outcomes.

Bottom line: In a systematic review, interdisciplinary team care in general medical wards is not associated with reduced complications, length of stay, readmissions, or mortality.

Citation: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards: a systematic review. JAMA Intern Med. 2015;175(8):1288-1298.

Clinical question: Does interdisciplinary care on general medical wards improve patient outcomes?

Background: Patients on general medical wards might experience errors and/or preventable deaths. One mechanism that could reduce the risk of errors or preventable death is the utilization of interdisciplinary team care.

Study design: Systematic review.

Setting: Studies published in English from 1998 through 2013 in Embase, MEDLINE, and PsycINFO.

Synopsis: Reports of interdisciplinary team care interventions on general medical wards in which the care was evaluated against an objective patient outcome were reviewed. Outcomes were grouped into early (less than 30 days) or late (30 days to 12 months). Thirty studies of more than 66,000 total patients were included; these were composed of RCTs, nonrandomized cluster trials, and controlled before-after studies.

Interventions either altered the composition of the care team or addressed the logistics of team practice. Studies evaluated complications of care, length of stay, readmissions, and mortality. Although some evidence showed interdisciplinary care reduces complications, the majority of studies did not show significant improvements in any other outcomes.

Bottom line: In a systematic review, interdisciplinary team care in general medical wards is not associated with reduced complications, length of stay, readmissions, or mortality.

Citation: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards: a systematic review. JAMA Intern Med. 2015;175(8):1288-1298.

Clinical question: Does interdisciplinary care on general medical wards improve patient outcomes?

Background: Patients on general medical wards might experience errors and/or preventable deaths. One mechanism that could reduce the risk of errors or preventable death is the utilization of interdisciplinary team care.

Study design: Systematic review.

Setting: Studies published in English from 1998 through 2013 in Embase, MEDLINE, and PsycINFO.

Synopsis: Reports of interdisciplinary team care interventions on general medical wards in which the care was evaluated against an objective patient outcome were reviewed. Outcomes were grouped into early (less than 30 days) or late (30 days to 12 months). Thirty studies of more than 66,000 total patients were included; these were composed of RCTs, nonrandomized cluster trials, and controlled before-after studies.

Interventions either altered the composition of the care team or addressed the logistics of team practice. Studies evaluated complications of care, length of stay, readmissions, and mortality. Although some evidence showed interdisciplinary care reduces complications, the majority of studies did not show significant improvements in any other outcomes.

Bottom line: In a systematic review, interdisciplinary team care in general medical wards is not associated with reduced complications, length of stay, readmissions, or mortality.

Citation: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards: a systematic review. JAMA Intern Med. 2015;175(8):1288-1298.

Clinical question: Is there an association between objective measures of surgical quality and patient satisfaction as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey?

Background: The Centers for Medicare and Medicaid Services (CMS) has tied financial reimbursement to patient satisfaction scores. It is unknown whether high-quality surgery correlates with higher patient satisfaction scores.

Study design: Retrospective, observational study.

Setting: One hundred eighty hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).

Synopsis: The study included 103,866 Medicare patients 65 and older who had surgery at a participating ACS NSQIP hospital between 2004-2008. Data regarding these patients were collected from a linked database (including Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare). Analysis of five 30-day outcomes was performed in order to assess surgical quality:

• Post-operative mortality;
• Major complication;
• Minor complication;
• Death following a complication; and
• Readmission.

Participating hospitals were grouped into quartiles based upon their performance on the HCAHPS survey.

Hospitals that performed in the highest quartile on the HCAHPS survey had significantly lower 30-day mortality, death following complications, and minor complications. No differences were detected in hospital readmissions or major complications based on patient satisfaction.

The results of this study may not be generalizable to all hospitals given the fact that the dataset is from Medicare patients only and participation in the ACS NSQIP is voluntary.

Bottom line: Using data from a national database, researchers found a positive association between patient satisfaction scores and objective measures of surgical quality.

Citation: Sacks GD, Lawson EH, Dawes AJ, et al. Relationship between hospital performance on a patient satisfaction survey and surgical quality [published online ahead of print June 24, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.1108.

Clinical question: Is there an association between objective measures of surgical quality and patient satisfaction as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey?

Background: The Centers for Medicare and Medicaid Services (CMS) has tied financial reimbursement to patient satisfaction scores. It is unknown whether high-quality surgery correlates with higher patient satisfaction scores.

Study design: Retrospective, observational study.

Setting: One hundred eighty hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).

Synopsis: The study included 103,866 Medicare patients 65 and older who had surgery at a participating ACS NSQIP hospital between 2004-2008. Data regarding these patients were collected from a linked database (including Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare). Analysis of five 30-day outcomes was performed in order to assess surgical quality:

• Post-operative mortality;
• Major complication;
• Minor complication;
• Death following a complication; and
• Readmission.

Participating hospitals were grouped into quartiles based upon their performance on the HCAHPS survey.

Hospitals that performed in the highest quartile on the HCAHPS survey had significantly lower 30-day mortality, death following complications, and minor complications. No differences were detected in hospital readmissions or major complications based on patient satisfaction.

The results of this study may not be generalizable to all hospitals given the fact that the dataset is from Medicare patients only and participation in the ACS NSQIP is voluntary.

Bottom line: Using data from a national database, researchers found a positive association between patient satisfaction scores and objective measures of surgical quality.

Citation: Sacks GD, Lawson EH, Dawes AJ, et al. Relationship between hospital performance on a patient satisfaction survey and surgical quality [published online ahead of print June 24, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.1108.

Clinical question: Is there an association between objective measures of surgical quality and patient satisfaction as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey?

Background: The Centers for Medicare and Medicaid Services (CMS) has tied financial reimbursement to patient satisfaction scores. It is unknown whether high-quality surgery correlates with higher patient satisfaction scores.

Study design: Retrospective, observational study.

Setting: One hundred eighty hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP).

Synopsis: The study included 103,866 Medicare patients 65 and older who had surgery at a participating ACS NSQIP hospital between 2004-2008. Data regarding these patients were collected from a linked database (including Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare). Analysis of five 30-day outcomes was performed in order to assess surgical quality:

• Post-operative mortality;
• Major complication;
• Minor complication;
• Death following a complication; and
• Readmission.

Participating hospitals were grouped into quartiles based upon their performance on the HCAHPS survey.

Hospitals that performed in the highest quartile on the HCAHPS survey had significantly lower 30-day mortality, death following complications, and minor complications. No differences were detected in hospital readmissions or major complications based on patient satisfaction.

The results of this study may not be generalizable to all hospitals given the fact that the dataset is from Medicare patients only and participation in the ACS NSQIP is voluntary.

Bottom line: Using data from a national database, researchers found a positive association between patient satisfaction scores and objective measures of surgical quality.

Citation: Sacks GD, Lawson EH, Dawes AJ, et al. Relationship between hospital performance on a patient satisfaction survey and surgical quality [published online ahead of print June 24, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.1108.