Thrombus

Credit: Andre E.X. Brown

CHICAGO—An experimental agent known as andexanet alfa can reverse the anticoagulant effect of apixaban in healthy volunteers, a phase 3 study suggests.

All subjects who received andexanet alfa after treatment with apixaban exhibited at least a 90% reversal of anti‐factor Xa activity, and thrombin generation was restored to baseline levels.

None of the subjects experienced serious adverse events or thrombotic events, and none developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented these results at the American Heart Association 2014 Scientific Sessions. Dr Crowther is a consultant for Portola Pharmaceuticals, the makers of andexanet alfa.

Andexanet alfa is a recombinant, modified factor Xa molecule. It is being developed as an antidote for patients receiving a factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery.

In the phase 3 ANNEXA-A study, researchers evaluated the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers.

Dr Crowther presented results from the first part of the study, which included 33 subjects ages 50 to 73. The subjects received apixaban at 5 mg twice daily for 4 days. Then, they were randomized in a 3:1 ratio to receive andexanet alfa as a 400 mg intravenous bolus (n=24) or placebo (n=9).

Two to 5 minutes after subjects received andexanet alfa, the anticoagulant activity of apixaban was reversed by approximately 94% compared to placebo (P<0.0001). And the effect lasted 1 to 2 hours.

Every subject treated with andexanet alfa had between 90% and 96% reversal of the anticoagulant activity of apixaban. The reversal of anti-factor Xa activity was correlated with a significant reduction in the level of free, unbound apixaban in the plasma (P<0.0001).

In addition, andexanet alfa restored thrombin generation to baseline levels. And there was no rebound effect on thrombin generation after andexanet and/or apixaban were cleared.

Three subjects experienced mild infusion reactions after receiving andexanet alfa. But there were no serious adverse events, thrombotic events, or antibodies to factor X or Xa reported.

Now, researchers are going ahead with the second part of the ANNEXA-A study, hoping to demonstrate

that prolonged reversal can be sustained with a continuous infusion of andexanet alfa after the bolus dose.

Thirty-two healthy volunteers will receive apixaban at 5 mg twice daily for 4 days and then be randomized to placebo or andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes. Data from this part of the study are expected to be available in early 2015.

Thrombus

Credit: Andre E.X. Brown

CHICAGO—An experimental agent known as andexanet alfa can reverse the anticoagulant effect of apixaban in healthy volunteers, a phase 3 study suggests.

All subjects who received andexanet alfa after treatment with apixaban exhibited at least a 90% reversal of anti‐factor Xa activity, and thrombin generation was restored to baseline levels.

None of the subjects experienced serious adverse events or thrombotic events, and none developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented these results at the American Heart Association 2014 Scientific Sessions. Dr Crowther is a consultant for Portola Pharmaceuticals, the makers of andexanet alfa.

Andexanet alfa is a recombinant, modified factor Xa molecule. It is being developed as an antidote for patients receiving a factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery.

In the phase 3 ANNEXA-A study, researchers evaluated the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers.

Dr Crowther presented results from the first part of the study, which included 33 subjects ages 50 to 73. The subjects received apixaban at 5 mg twice daily for 4 days. Then, they were randomized in a 3:1 ratio to receive andexanet alfa as a 400 mg intravenous bolus (n=24) or placebo (n=9).

Two to 5 minutes after subjects received andexanet alfa, the anticoagulant activity of apixaban was reversed by approximately 94% compared to placebo (P<0.0001). And the effect lasted 1 to 2 hours.

Every subject treated with andexanet alfa had between 90% and 96% reversal of the anticoagulant activity of apixaban. The reversal of anti-factor Xa activity was correlated with a significant reduction in the level of free, unbound apixaban in the plasma (P<0.0001).

In addition, andexanet alfa restored thrombin generation to baseline levels. And there was no rebound effect on thrombin generation after andexanet and/or apixaban were cleared.

Three subjects experienced mild infusion reactions after receiving andexanet alfa. But there were no serious adverse events, thrombotic events, or antibodies to factor X or Xa reported.

Now, researchers are going ahead with the second part of the ANNEXA-A study, hoping to demonstrate

that prolonged reversal can be sustained with a continuous infusion of andexanet alfa after the bolus dose.

Thirty-two healthy volunteers will receive apixaban at 5 mg twice daily for 4 days and then be randomized to placebo or andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes. Data from this part of the study are expected to be available in early 2015.

Thrombus

Credit: Andre E.X. Brown

CHICAGO—An experimental agent known as andexanet alfa can reverse the anticoagulant effect of apixaban in healthy volunteers, a phase 3 study suggests.

All subjects who received andexanet alfa after treatment with apixaban exhibited at least a 90% reversal of anti‐factor Xa activity, and thrombin generation was restored to baseline levels.

None of the subjects experienced serious adverse events or thrombotic events, and none developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented these results at the American Heart Association 2014 Scientific Sessions. Dr Crowther is a consultant for Portola Pharmaceuticals, the makers of andexanet alfa.

Andexanet alfa is a recombinant, modified factor Xa molecule. It is being developed as an antidote for patients receiving a factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery.

In the phase 3 ANNEXA-A study, researchers evaluated the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers.

Dr Crowther presented results from the first part of the study, which included 33 subjects ages 50 to 73. The subjects received apixaban at 5 mg twice daily for 4 days. Then, they were randomized in a 3:1 ratio to receive andexanet alfa as a 400 mg intravenous bolus (n=24) or placebo (n=9).

Two to 5 minutes after subjects received andexanet alfa, the anticoagulant activity of apixaban was reversed by approximately 94% compared to placebo (P<0.0001). And the effect lasted 1 to 2 hours.

Every subject treated with andexanet alfa had between 90% and 96% reversal of the anticoagulant activity of apixaban. The reversal of anti-factor Xa activity was correlated with a significant reduction in the level of free, unbound apixaban in the plasma (P<0.0001).

In addition, andexanet alfa restored thrombin generation to baseline levels. And there was no rebound effect on thrombin generation after andexanet and/or apixaban were cleared.

Three subjects experienced mild infusion reactions after receiving andexanet alfa. But there were no serious adverse events, thrombotic events, or antibodies to factor X or Xa reported.

Now, researchers are going ahead with the second part of the ANNEXA-A study, hoping to demonstrate

that prolonged reversal can be sustained with a continuous infusion of andexanet alfa after the bolus dose.

Thirty-two healthy volunteers will receive apixaban at 5 mg twice daily for 4 days and then be randomized to placebo or andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes. Data from this part of the study are expected to be available in early 2015.

Lab mouse

Scientists believe they’ve devised a way to use antimiRs as anticancer drugs by showing that a specific antimiR could treat diffuse large B-cell lymphoma (DLBCL) in mice.

In a letter to Nature, the group explained that microRNAs known as oncomiRs can play a causal role in the onset and maintenance of cancer when they are overexpressed.

So inhibiting oncomiRs using antisense oligomers, or antimiRs, has seemed a promising therapeutic strategy. But physiological and cellular barriers have prevented targeted delivery.

Frank Slack, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, and his colleagues have devised a new antimiR delivery platform and shown that it can inhibit DLBCL growth in vivo.

The team created a mouse model to study miR-155, an oncomiR that, when overexpressed, leads to DLBCL.

“We hypothesized that we could inhibit the function of miR-155 by way of an antisense molecule that would bind to miR-155,” Dr Slack said. “[However,] there are a number of significant obstacles to reaching the tumor cell target. Some roadblocks are clearance through the kidneys and accumulation in the liver, which absorbs any systemically injected agent.”

“Furthermore, even if you are able to reach your targeted cells, the molecules must cross cell membranes and escape degradation from a process known as endocytosis. If you can picture our antisense molecule being a warhead, we had to find the right ‘rocket’ to actually transport it to its target.”

The “rocket” turned out to be a peptide with a low-pH induced transmembrane structure (pHLIP), meaning it inserts into cell membranes only when cells are low in pH. And tumor cells provided the ideal environment.

“When we attached our antisense warhead to the pHLIP peptide, not only did it successfully insert itself into the tumor cell, but it also dragged the antisense molecule itself into the cell,” Dr Slack said. “Now the ‘warhead’ could deploy and actually inhibit microRNA function and control cancer growth.”

In the miR-155/DLBCL mouse models, pHLIP-anti155 slowed tumor growth, suppressed the metastatic spread of neoplastic lymphocytes to other organs, reduced the onset of splenomegaly, and delayed the development of conspicuous lymphadenopathy, when compared to control mice.

Responses with pHLIP-anti155 were similar to those observed in mice that received doxorubicin or CHOP, but pHLIP-anti155 proved less toxic than the other treatments.

“With this delivery platform, we should also be able to transform other RNAs into druggable targets,” Dr Slack said, adding that low pH is also an issue in kidney disease, myocardial infarction, stroke, and infection, among other conditions. So this type of therapy could have wide applications.

Lab mouse

Scientists believe they’ve devised a way to use antimiRs as anticancer drugs by showing that a specific antimiR could treat diffuse large B-cell lymphoma (DLBCL) in mice.

In a letter to Nature, the group explained that microRNAs known as oncomiRs can play a causal role in the onset and maintenance of cancer when they are overexpressed.

So inhibiting oncomiRs using antisense oligomers, or antimiRs, has seemed a promising therapeutic strategy. But physiological and cellular barriers have prevented targeted delivery.

Frank Slack, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, and his colleagues have devised a new antimiR delivery platform and shown that it can inhibit DLBCL growth in vivo.

The team created a mouse model to study miR-155, an oncomiR that, when overexpressed, leads to DLBCL.

“We hypothesized that we could inhibit the function of miR-155 by way of an antisense molecule that would bind to miR-155,” Dr Slack said. “[However,] there are a number of significant obstacles to reaching the tumor cell target. Some roadblocks are clearance through the kidneys and accumulation in the liver, which absorbs any systemically injected agent.”

“Furthermore, even if you are able to reach your targeted cells, the molecules must cross cell membranes and escape degradation from a process known as endocytosis. If you can picture our antisense molecule being a warhead, we had to find the right ‘rocket’ to actually transport it to its target.”

The “rocket” turned out to be a peptide with a low-pH induced transmembrane structure (pHLIP), meaning it inserts into cell membranes only when cells are low in pH. And tumor cells provided the ideal environment.

“When we attached our antisense warhead to the pHLIP peptide, not only did it successfully insert itself into the tumor cell, but it also dragged the antisense molecule itself into the cell,” Dr Slack said. “Now the ‘warhead’ could deploy and actually inhibit microRNA function and control cancer growth.”

In the miR-155/DLBCL mouse models, pHLIP-anti155 slowed tumor growth, suppressed the metastatic spread of neoplastic lymphocytes to other organs, reduced the onset of splenomegaly, and delayed the development of conspicuous lymphadenopathy, when compared to control mice.

Responses with pHLIP-anti155 were similar to those observed in mice that received doxorubicin or CHOP, but pHLIP-anti155 proved less toxic than the other treatments.

“With this delivery platform, we should also be able to transform other RNAs into druggable targets,” Dr Slack said, adding that low pH is also an issue in kidney disease, myocardial infarction, stroke, and infection, among other conditions. So this type of therapy could have wide applications.

Lab mouse

Scientists believe they’ve devised a way to use antimiRs as anticancer drugs by showing that a specific antimiR could treat diffuse large B-cell lymphoma (DLBCL) in mice.

In a letter to Nature, the group explained that microRNAs known as oncomiRs can play a causal role in the onset and maintenance of cancer when they are overexpressed.

So inhibiting oncomiRs using antisense oligomers, or antimiRs, has seemed a promising therapeutic strategy. But physiological and cellular barriers have prevented targeted delivery.

Frank Slack, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, and his colleagues have devised a new antimiR delivery platform and shown that it can inhibit DLBCL growth in vivo.

The team created a mouse model to study miR-155, an oncomiR that, when overexpressed, leads to DLBCL.

“We hypothesized that we could inhibit the function of miR-155 by way of an antisense molecule that would bind to miR-155,” Dr Slack said. “[However,] there are a number of significant obstacles to reaching the tumor cell target. Some roadblocks are clearance through the kidneys and accumulation in the liver, which absorbs any systemically injected agent.”

“Furthermore, even if you are able to reach your targeted cells, the molecules must cross cell membranes and escape degradation from a process known as endocytosis. If you can picture our antisense molecule being a warhead, we had to find the right ‘rocket’ to actually transport it to its target.”

The “rocket” turned out to be a peptide with a low-pH induced transmembrane structure (pHLIP), meaning it inserts into cell membranes only when cells are low in pH. And tumor cells provided the ideal environment.

“When we attached our antisense warhead to the pHLIP peptide, not only did it successfully insert itself into the tumor cell, but it also dragged the antisense molecule itself into the cell,” Dr Slack said. “Now the ‘warhead’ could deploy and actually inhibit microRNA function and control cancer growth.”

In the miR-155/DLBCL mouse models, pHLIP-anti155 slowed tumor growth, suppressed the metastatic spread of neoplastic lymphocytes to other organs, reduced the onset of splenomegaly, and delayed the development of conspicuous lymphadenopathy, when compared to control mice.

Responses with pHLIP-anti155 were similar to those observed in mice that received doxorubicin or CHOP, but pHLIP-anti155 proved less toxic than the other treatments.

“With this delivery platform, we should also be able to transform other RNAs into druggable targets,” Dr Slack said, adding that low pH is also an issue in kidney disease, myocardial infarction, stroke, and infection, among other conditions. So this type of therapy could have wide applications.

Blood for transfusion

Engineers have devised a method that could allow for faster preparation of frozen red blood cells (RBCs), according to research published in Biomicrofluidics.

It’s already possible to cryopreserve RBCs in the presence of 40% glycerol, but the post-thaw washing process can take an hour or more.

Initial experiments and computer modeling suggest this process can be streamlined to take as little as 3 minutes, using a membrane-based microfluidic device.

This could make it more feasible to use frozen blood in emergency or time-constrained medical situations.

“Only a small fraction of our blood supply is now frozen because it’s often impractical to wait so long when a transfusion is needed immediately,” said study author Adam Higgins, PhD, of Oregon State University in Corvallis.

“Because of that, our entire system depends on constantly balancing the use and supply of blood products that can only last 6 weeks or less with refrigeration. This is difficult and can lead to loss of outdated blood, periodic shortages, and other inefficiencies that could be solved with the use of frozen blood.”

With this in mind, the researchers explored the potential for rapid glycerol extraction using a membrane-based microfluidic device.

They theorized that extremely tiny microchannel plates and membranes could be used to precisely control the removal of glycerol at a time scale of seconds, without causing excessive osmotic damage.

The team developed a mass transfer model that allowed them to predict glycerol removal, as well as the resulting cell volume changes.

Results of the researchers’ experiments were in line with the predictions and suggest it is possible to reduce the glycerol concentration by more than 50% without excessive hemolysis.

Now, the team hopes to create working prototypes of the needed technology for further development and testing of this concept. They believe an optimized process may be even faster than the 3 minutes now being predicted.

Blood for transfusion

Engineers have devised a method that could allow for faster preparation of frozen red blood cells (RBCs), according to research published in Biomicrofluidics.

It’s already possible to cryopreserve RBCs in the presence of 40% glycerol, but the post-thaw washing process can take an hour or more.

Initial experiments and computer modeling suggest this process can be streamlined to take as little as 3 minutes, using a membrane-based microfluidic device.

This could make it more feasible to use frozen blood in emergency or time-constrained medical situations.

“Only a small fraction of our blood supply is now frozen because it’s often impractical to wait so long when a transfusion is needed immediately,” said study author Adam Higgins, PhD, of Oregon State University in Corvallis.

“Because of that, our entire system depends on constantly balancing the use and supply of blood products that can only last 6 weeks or less with refrigeration. This is difficult and can lead to loss of outdated blood, periodic shortages, and other inefficiencies that could be solved with the use of frozen blood.”

With this in mind, the researchers explored the potential for rapid glycerol extraction using a membrane-based microfluidic device.

They theorized that extremely tiny microchannel plates and membranes could be used to precisely control the removal of glycerol at a time scale of seconds, without causing excessive osmotic damage.

The team developed a mass transfer model that allowed them to predict glycerol removal, as well as the resulting cell volume changes.

Results of the researchers’ experiments were in line with the predictions and suggest it is possible to reduce the glycerol concentration by more than 50% without excessive hemolysis.

Now, the team hopes to create working prototypes of the needed technology for further development and testing of this concept. They believe an optimized process may be even faster than the 3 minutes now being predicted.

Blood for transfusion

Engineers have devised a method that could allow for faster preparation of frozen red blood cells (RBCs), according to research published in Biomicrofluidics.

It’s already possible to cryopreserve RBCs in the presence of 40% glycerol, but the post-thaw washing process can take an hour or more.

Initial experiments and computer modeling suggest this process can be streamlined to take as little as 3 minutes, using a membrane-based microfluidic device.

This could make it more feasible to use frozen blood in emergency or time-constrained medical situations.

“Only a small fraction of our blood supply is now frozen because it’s often impractical to wait so long when a transfusion is needed immediately,” said study author Adam Higgins, PhD, of Oregon State University in Corvallis.

“Because of that, our entire system depends on constantly balancing the use and supply of blood products that can only last 6 weeks or less with refrigeration. This is difficult and can lead to loss of outdated blood, periodic shortages, and other inefficiencies that could be solved with the use of frozen blood.”

With this in mind, the researchers explored the potential for rapid glycerol extraction using a membrane-based microfluidic device.

They theorized that extremely tiny microchannel plates and membranes could be used to precisely control the removal of glycerol at a time scale of seconds, without causing excessive osmotic damage.

The team developed a mass transfer model that allowed them to predict glycerol removal, as well as the resulting cell volume changes.

Results of the researchers’ experiments were in line with the predictions and suggest it is possible to reduce the glycerol concentration by more than 50% without excessive hemolysis.

Now, the team hopes to create working prototypes of the needed technology for further development and testing of this concept. They believe an optimized process may be even faster than the 3 minutes now being predicted.

Blood samples

Credit: Graham Colm

A new test can detect bloodstream infections with “unprecedented” speed and accuracy, according to researchers.

The group developed a test called Integrated Comprehensive Droplet Digital Detection (IC 3D).

And experiments showed that IC 3D can detect bacteria in milliliters of blood with single-cell sensitivity in 1.5 to 4 hours, with no cell culture necessary.

The researchers described this test in Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” said study author Weian Zhao, PhD, of the University of California Irvine (UCI).

“As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV, and, most notably, Ebola.”

Worldwide, more than 2 million people a year get antibiotic-resistant blood infections, and 23,000 of them die, according to the US Centers for Disease Control & Prevention. This high mortality rate is due, in part, to the inability to diagnose and treat patients in the early stages.

Recent molecular diagnostic methods can reduce the assay time to hours but may not be sensitive enough to detect bacteria that occur at low concentrations in blood.

The IC 3D technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal.

Dr Zhao said that separating the samples into so many small droplets minimizes the interference of other components in blood, making it possible to directly detect target bacteria without the purification typically required in conventional assays.

To identify bacteria-containing droplets among billions of others in a timely fashion, Dr Zhao and his colleagues incorporated a 3-dimensional particle counter developed by UCI biomedical engineer Enrico Gratton, PhD, and his colleagues that tags fluorescent particles within several minutes.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Dr Gratton said. “Importantly, using this technique, we can detect a positive hit with very high confidence.”

The researchers reported that IC 3D provided absolute quantification of stock and clinical isolates of Escherichia coli at a wide range of concentrations, from 1 to 10,000 bacteria per mL, in 1.5 to 4 hours.

A UCI spinoff, Velox Biosystems, is now developing the IC 3D technology.

Blood samples

Credit: Graham Colm

A new test can detect bloodstream infections with “unprecedented” speed and accuracy, according to researchers.

The group developed a test called Integrated Comprehensive Droplet Digital Detection (IC 3D).

And experiments showed that IC 3D can detect bacteria in milliliters of blood with single-cell sensitivity in 1.5 to 4 hours, with no cell culture necessary.

The researchers described this test in Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” said study author Weian Zhao, PhD, of the University of California Irvine (UCI).

“As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV, and, most notably, Ebola.”

Worldwide, more than 2 million people a year get antibiotic-resistant blood infections, and 23,000 of them die, according to the US Centers for Disease Control & Prevention. This high mortality rate is due, in part, to the inability to diagnose and treat patients in the early stages.

Recent molecular diagnostic methods can reduce the assay time to hours but may not be sensitive enough to detect bacteria that occur at low concentrations in blood.

The IC 3D technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal.

Dr Zhao said that separating the samples into so many small droplets minimizes the interference of other components in blood, making it possible to directly detect target bacteria without the purification typically required in conventional assays.

To identify bacteria-containing droplets among billions of others in a timely fashion, Dr Zhao and his colleagues incorporated a 3-dimensional particle counter developed by UCI biomedical engineer Enrico Gratton, PhD, and his colleagues that tags fluorescent particles within several minutes.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Dr Gratton said. “Importantly, using this technique, we can detect a positive hit with very high confidence.”

The researchers reported that IC 3D provided absolute quantification of stock and clinical isolates of Escherichia coli at a wide range of concentrations, from 1 to 10,000 bacteria per mL, in 1.5 to 4 hours.

A UCI spinoff, Velox Biosystems, is now developing the IC 3D technology.

Blood samples

Credit: Graham Colm

A new test can detect bloodstream infections with “unprecedented” speed and accuracy, according to researchers.

The group developed a test called Integrated Comprehensive Droplet Digital Detection (IC 3D).

And experiments showed that IC 3D can detect bacteria in milliliters of blood with single-cell sensitivity in 1.5 to 4 hours, with no cell culture necessary.

The researchers described this test in Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” said study author Weian Zhao, PhD, of the University of California Irvine (UCI).

“As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV, and, most notably, Ebola.”

Worldwide, more than 2 million people a year get antibiotic-resistant blood infections, and 23,000 of them die, according to the US Centers for Disease Control & Prevention. This high mortality rate is due, in part, to the inability to diagnose and treat patients in the early stages.

Recent molecular diagnostic methods can reduce the assay time to hours but may not be sensitive enough to detect bacteria that occur at low concentrations in blood.

The IC 3D technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal.

Dr Zhao said that separating the samples into so many small droplets minimizes the interference of other components in blood, making it possible to directly detect target bacteria without the purification typically required in conventional assays.

To identify bacteria-containing droplets among billions of others in a timely fashion, Dr Zhao and his colleagues incorporated a 3-dimensional particle counter developed by UCI biomedical engineer Enrico Gratton, PhD, and his colleagues that tags fluorescent particles within several minutes.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Dr Gratton said. “Importantly, using this technique, we can detect a positive hit with very high confidence.”

The researchers reported that IC 3D provided absolute quantification of stock and clinical isolates of Escherichia coli at a wide range of concentrations, from 1 to 10,000 bacteria per mL, in 1.5 to 4 hours.

A UCI spinoff, Velox Biosystems, is now developing the IC 3D technology.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

PRACTICE CHANGER
Ensure that antibiotics are administered to surgical patients when their urinary catheter is removed to reduce the risk for urinary tract infections (UTIs).¹

STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis.¹

ILLUSTRATIVE CASE
A 49-year-old man was admitted to the hospital for resection of a vertebral mass. He is almost ready for discharge, and soon his urinary catheter will be removed. Should he be given an antibiotic when his catheter is removed to prevent a UTI?

Approximately 15% to 25% of hospitalized patients receive a urinary catheter, typically during the perioperative period.² UTIs are the most common hospital-acquired infections, and virtually all of these UTIs are caused by instrumentation of the urinary tract, primarily by catheters.²

Although the mortality rate among patients with catheter-associated UTIs (CAUTIs) is just 2.3%, CAUTIs are the leading cause of hospital-acquired bacteremia, which increases morbidity and length of stay.² The most ­common pathogens for CAUTIs are Escherichia coli (21.4%), Candida species (21%), and Enterococcus species (14.9%).²Pseudomonas aeruginosa, Klebsiella, and Enterobacter species comprise the bulk of the remainder.²

Support for antibiotic prophylaxis has historically been equivocal
Until now, no data clearly supported routine use of prophylactic antibiotics after urinary catheterization. CDC guidelines published in 2009 outline which patients are appropriate candidates for catheterization but do not recommend routine use of antibiotics to prevent CAUTIs.² A 2014 Infectious Diseases Society of America practice recommendation, which was published after the study reported on here, states the benefit of antibiotics at the time of catheter removal is an unresolved issue.³

STUDY SUMMARY
Analysis shows prophylactic antibiotics reduce UTIs
Marschall et al¹ searched multiple databases for studies published between 1947 and 2012 that evaluated prophylactic use of antibiotics at the time of urinary catheter removal. The endpoint for their analysis was symptomatic UTI, which they defined as bacteriuria plus at least one clinical symptom. Trials were excluded if patients had suprapubic catheters or if antibiotics were started shortly after the catheter was inserted.

The authors analyzed seven studies. Six were randomized controlled trials, of which one was unpublished. The seventh trial was a nonrandomized study that compared outcomes of patients of two surgeons, one of whom used prophylactic antibiotics and one who did not. Five studies enrolled surgical patients exclusively, including two that focused on urology patients. In all of the studies, patients had a urinary catheter in place for fewer than 15 days. The duration of antibiotic treatment varied from a single dose to three days. The antibiotics used included trimethoprim/sulfamethoxazole, nitrofurantoin, ciprofloxacin, and a cephalosporin.

Antibiotic prophylaxis significantly reduced the rate of ­CAUTIs. The absolute risk reduction was 5.8%; the rate of CAUTIs was 4.7% in the group treated with antibiotics and 10.5% in the control group. The number needed to treat to prevent one CAUTI was 17, with a risk ratio (RR) of .45. The RR varied only slightly (.36) when the researchers repeated their analysis but excluded the unpublished trial and remained at .45 when they analyzed only studies of surgical patients.

The reduction in CAUTIs remained consistent despite varying lengths of antibiotic administration and choice of antimicrobial agents. However, when the authors looked at pooled results just from the two studies that included both surgical and medical patients, they found no decrease in CAUTIs.

WHAT’S NEW
We now have an effective way to reduce CAUTIs
Prophylactic use of antibiotics when a urinary catheter is removed appears to reduce the rate of CAUTIs by more than 50% in surgical patients. The 2009 CDC guidelines on CAUTI prevention emphasize the use of appropriate infection control measures and limiting the duration of urinary catheter use.² Now there are data showing a reduction in the incidence of CAUTIs when prophylactic antibiotics are given during catheter removal.

Continue for caveats and challenges >>

CAVEATS
Results may not apply to ­nonsurgical patients
This meta-analysis does not provide enough information to identify which patients are most likely to benefit from antibiotic prophylaxis. Most patients (92%) in this analysis had undergone surgery, but urinary catheterization is common among medically hospitalized patients. Studies of antibiotic prophylaxis at the time of catheter removal in nonsurgical patients are needed to strengthen the recommendation of this practice for all patients.

Some of the studies analyzed may have been biased. The authors determined that most of the studies in their meta-analysis were at high risk for attrition bias because there was potential for systematic differences in withdrawals between the treatment and control groups. In addition, in most studies, the randomization and allocation appeared to be inadequate, which increased the risk for selection bias.

CHALLENGES TO IMPLEMENTATION
Which antibiotics to use—and for how long—remains unclear
Antibiotic choice depends upon institutional policies and local resistance patterns, which complicates making universal recommendations. The optimal duration of treatment also is unknown, although this meta-analysis suggests that prophylaxis for three days or less can reduce CAUTI risk.

Catheters impregnated with antimicrobials or with microbial resistance barriers may be an alternative to administration of antibiotics at catheter removal, but in preliminary studies, these devices have not been shown to reduce the incidence of CAUTIs.^4,5 Increasing antimicrobial resistance also complicates the widespread use of prophylaxis.

REFERENCES
1. Marschall J, Carpenter CR, Fowler S, et al; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013;346:f3147.

2. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. www.cdc.gov/hicpac/pdf/cauti/cautiguideline2009final.pdf. Accessed November 12, 2014.  

3. Lo E, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:464-479.

4. Pickard R, Lam T, Maclennan G, et al. Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial). Health Technol Assess. 2012;16:1-197.

5. Pickard R, Lam T, MacLennan G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet. 2012;380:1927-1935.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):E10-E12.

A 17-year-old girl underwent a routine tonsillectomy without complications at a surgical center. Following the procedure, she was taken to the recovery room and administered fentanyl for pain. 

The recovery room nurse assigned to monitor the patient spent 20 minutes treating another patient and then went on break, signing out to a second recovery room nurse. On receiving the sign­out, the second recovery room nurse discovered that the patient was in respiratory distress and began resuscitation efforts. The patient was resuscitated but died 15 days later.

The plaintiff claimed that the girl was left unmonitored by nurses assigned to the unit and that the monitoring equipment was not used, not set properly, or muted.
During her deposition, the second recovery room nurse admitted under oath that the first recovery room nurse falsified the patient’s chart; the first nurse claimed that she had assessed the patient during an important time period when she had not.  

Continue for the outcome and commentary >>

OUTCOME
The case was settled for $6 million: $1 million against the surgical center’s primary policy and $5 million against its excess policy.

COMMENT
Cases such as this one are unfortunate and avoidable—and tragically, too common. On any medical malpractice lawyer’s desk is a teetering stack of potential cases; much of that stack involves narcotics. This case raises two important areas to discuss: the dangers of parenteral narcotics and the perils of falsifying medical records.

First, when parenteral narcotics are given, proper monitoring safeguards must be in place. Malpractice cases frequently involve a scenario in which patients are given parenteral narcotics and left alone, out of sight, and unmonitored. This simply can’t be done. Close supervision and monitoring—with both equipment and eyes—are required to safeguard your patients and avoid malpractice risk. 

Other malpractice scenarios involve the ambulatory patient who is given parenteral narcotics in a clinic setting and discharged after a 10-minute “observation” period—a period during which peak drug effect is probably not realized. The patient is unsafely discharged before that peak is reached and suffers potentially fatal adverse effects. Even when direct fatal effects are not realized, the patient is discharged with impaired motor coordination and cognitive judgment, placing the patient at risk in his/her surroundings.

If a clinician commits to giving parenteral narcotics, he or she commits to providing “real-time” monitoring until the narcotic effects have safely diminished and the patient’s condition is thoroughly documented in the record. Generally speaking, the patient must be reasonably clear of the effects of narcotics before discharge. (Remember the special case of naloxone, administered for opiate excesses, in which naloxone is metabolized before the opiate; the patient can relapse into a coma/apnea if the naloxone fully metabolizes before the opiate.)

Here, this young woman was probably opiate naïve. While the amount she was given was certain, her response to the drug was not. She was left alone for at least 20 minutes and did not have a functioning SaO₂ monitor. Close monitoring of this patient was required but not provided.

As a result of this case, the surgical center changed several policies: Nurses must be on a one-to-one ratio with patients who have received narcotics during anesthesia. Furthermore, nurses must have line-of-sight to see patients at all times and, importantly, may not mute monitors (eg, oximetry monitors). 

The second salient point of this case is never, ever alter or falsify patient records! It will be discovered, and your credibility will be irretrievably damaged. Plaintiff lawyers live for this, and yet clinicians continue to do it. Don’t.

When altered medical records are discovered, the plaintiff’s theory of the case will be “cover up,” and jurors will be invited to punish the clinician for it. The jurors will do so. 

Also problematic is an otherwise defensible case that becomes much more difficult to defend because a clinician has altered the records. Remember, the plaintiff must prove all aspects of negligence, including causation and damages. In some cases, the clinician knows an obvious mistake was made but does not know that the eventual damages may be minimal or attributable to another cause. By altering the medical record, the clinician may enhance the damages value of a case by introducing a punitive element. Altering records may result in a lawsuit being filed when it otherwise wouldn’t have, or maintained when it would have been dropped before trial. In sum, don’t create a case against yourself by altering the medical records. 

Here, the falsification of records came to light during the deposition of the second nurse—who, being under oath, probably had little choice but to testify that the first nurse falsified the records. No doubt, this falsification made a bad case worse and gave the plaintiff leverage in securing more favorable settlement terms. 

You can’t make it right by rewriting history, but you can make it right by showing concern for the patient in your actions following a problem. You can also make it right by troubleshooting problems in a closed-door, formal peer review conference. Peer review conferences are designed for full and frank communication between clinicians and staff to solve problems, and as such they are protected from plaintiff disclosure.

This is an unfortunate case and a tragic loss of life. As clinicians, we must respect the potential life-ending power of parenteral narcotics. —DML

A 17-year-old girl underwent a routine tonsillectomy without complications at a surgical center. Following the procedure, she was taken to the recovery room and administered fentanyl for pain. 

The recovery room nurse assigned to monitor the patient spent 20 minutes treating another patient and then went on break, signing out to a second recovery room nurse. On receiving the sign­out, the second recovery room nurse discovered that the patient was in respiratory distress and began resuscitation efforts. The patient was resuscitated but died 15 days later.

The plaintiff claimed that the girl was left unmonitored by nurses assigned to the unit and that the monitoring equipment was not used, not set properly, or muted.
During her deposition, the second recovery room nurse admitted under oath that the first recovery room nurse falsified the patient’s chart; the first nurse claimed that she had assessed the patient during an important time period when she had not.  

Continue for the outcome and commentary >>

OUTCOME
The case was settled for $6 million: $1 million against the surgical center’s primary policy and $5 million against its excess policy.

COMMENT
Cases such as this one are unfortunate and avoidable—and tragically, too common. On any medical malpractice lawyer’s desk is a teetering stack of potential cases; much of that stack involves narcotics. This case raises two important areas to discuss: the dangers of parenteral narcotics and the perils of falsifying medical records.

First, when parenteral narcotics are given, proper monitoring safeguards must be in place. Malpractice cases frequently involve a scenario in which patients are given parenteral narcotics and left alone, out of sight, and unmonitored. This simply can’t be done. Close supervision and monitoring—with both equipment and eyes—are required to safeguard your patients and avoid malpractice risk. 

Other malpractice scenarios involve the ambulatory patient who is given parenteral narcotics in a clinic setting and discharged after a 10-minute “observation” period—a period during which peak drug effect is probably not realized. The patient is unsafely discharged before that peak is reached and suffers potentially fatal adverse effects. Even when direct fatal effects are not realized, the patient is discharged with impaired motor coordination and cognitive judgment, placing the patient at risk in his/her surroundings.

If a clinician commits to giving parenteral narcotics, he or she commits to providing “real-time” monitoring until the narcotic effects have safely diminished and the patient’s condition is thoroughly documented in the record. Generally speaking, the patient must be reasonably clear of the effects of narcotics before discharge. (Remember the special case of naloxone, administered for opiate excesses, in which naloxone is metabolized before the opiate; the patient can relapse into a coma/apnea if the naloxone fully metabolizes before the opiate.)

Here, this young woman was probably opiate naïve. While the amount she was given was certain, her response to the drug was not. She was left alone for at least 20 minutes and did not have a functioning SaO₂ monitor. Close monitoring of this patient was required but not provided.

As a result of this case, the surgical center changed several policies: Nurses must be on a one-to-one ratio with patients who have received narcotics during anesthesia. Furthermore, nurses must have line-of-sight to see patients at all times and, importantly, may not mute monitors (eg, oximetry monitors). 

The second salient point of this case is never, ever alter or falsify patient records! It will be discovered, and your credibility will be irretrievably damaged. Plaintiff lawyers live for this, and yet clinicians continue to do it. Don’t.

When altered medical records are discovered, the plaintiff’s theory of the case will be “cover up,” and jurors will be invited to punish the clinician for it. The jurors will do so. 

Also problematic is an otherwise defensible case that becomes much more difficult to defend because a clinician has altered the records. Remember, the plaintiff must prove all aspects of negligence, including causation and damages. In some cases, the clinician knows an obvious mistake was made but does not know that the eventual damages may be minimal or attributable to another cause. By altering the medical record, the clinician may enhance the damages value of a case by introducing a punitive element. Altering records may result in a lawsuit being filed when it otherwise wouldn’t have, or maintained when it would have been dropped before trial. In sum, don’t create a case against yourself by altering the medical records. 

Here, the falsification of records came to light during the deposition of the second nurse—who, being under oath, probably had little choice but to testify that the first nurse falsified the records. No doubt, this falsification made a bad case worse and gave the plaintiff leverage in securing more favorable settlement terms. 

You can’t make it right by rewriting history, but you can make it right by showing concern for the patient in your actions following a problem. You can also make it right by troubleshooting problems in a closed-door, formal peer review conference. Peer review conferences are designed for full and frank communication between clinicians and staff to solve problems, and as such they are protected from plaintiff disclosure.

This is an unfortunate case and a tragic loss of life. As clinicians, we must respect the potential life-ending power of parenteral narcotics. —DML

A 17-year-old girl underwent a routine tonsillectomy without complications at a surgical center. Following the procedure, she was taken to the recovery room and administered fentanyl for pain. 

The recovery room nurse assigned to monitor the patient spent 20 minutes treating another patient and then went on break, signing out to a second recovery room nurse. On receiving the sign­out, the second recovery room nurse discovered that the patient was in respiratory distress and began resuscitation efforts. The patient was resuscitated but died 15 days later.

The plaintiff claimed that the girl was left unmonitored by nurses assigned to the unit and that the monitoring equipment was not used, not set properly, or muted.
During her deposition, the second recovery room nurse admitted under oath that the first recovery room nurse falsified the patient’s chart; the first nurse claimed that she had assessed the patient during an important time period when she had not.  

Continue for the outcome and commentary >>

OUTCOME
The case was settled for $6 million: $1 million against the surgical center’s primary policy and $5 million against its excess policy.

COMMENT
Cases such as this one are unfortunate and avoidable—and tragically, too common. On any medical malpractice lawyer’s desk is a teetering stack of potential cases; much of that stack involves narcotics. This case raises two important areas to discuss: the dangers of parenteral narcotics and the perils of falsifying medical records.

First, when parenteral narcotics are given, proper monitoring safeguards must be in place. Malpractice cases frequently involve a scenario in which patients are given parenteral narcotics and left alone, out of sight, and unmonitored. This simply can’t be done. Close supervision and monitoring—with both equipment and eyes—are required to safeguard your patients and avoid malpractice risk. 

Other malpractice scenarios involve the ambulatory patient who is given parenteral narcotics in a clinic setting and discharged after a 10-minute “observation” period—a period during which peak drug effect is probably not realized. The patient is unsafely discharged before that peak is reached and suffers potentially fatal adverse effects. Even when direct fatal effects are not realized, the patient is discharged with impaired motor coordination and cognitive judgment, placing the patient at risk in his/her surroundings.

If a clinician commits to giving parenteral narcotics, he or she commits to providing “real-time” monitoring until the narcotic effects have safely diminished and the patient’s condition is thoroughly documented in the record. Generally speaking, the patient must be reasonably clear of the effects of narcotics before discharge. (Remember the special case of naloxone, administered for opiate excesses, in which naloxone is metabolized before the opiate; the patient can relapse into a coma/apnea if the naloxone fully metabolizes before the opiate.)

Here, this young woman was probably opiate naïve. While the amount she was given was certain, her response to the drug was not. She was left alone for at least 20 minutes and did not have a functioning SaO₂ monitor. Close monitoring of this patient was required but not provided.

As a result of this case, the surgical center changed several policies: Nurses must be on a one-to-one ratio with patients who have received narcotics during anesthesia. Furthermore, nurses must have line-of-sight to see patients at all times and, importantly, may not mute monitors (eg, oximetry monitors). 

The second salient point of this case is never, ever alter or falsify patient records! It will be discovered, and your credibility will be irretrievably damaged. Plaintiff lawyers live for this, and yet clinicians continue to do it. Don’t.

When altered medical records are discovered, the plaintiff’s theory of the case will be “cover up,” and jurors will be invited to punish the clinician for it. The jurors will do so. 

Also problematic is an otherwise defensible case that becomes much more difficult to defend because a clinician has altered the records. Remember, the plaintiff must prove all aspects of negligence, including causation and damages. In some cases, the clinician knows an obvious mistake was made but does not know that the eventual damages may be minimal or attributable to another cause. By altering the medical record, the clinician may enhance the damages value of a case by introducing a punitive element. Altering records may result in a lawsuit being filed when it otherwise wouldn’t have, or maintained when it would have been dropped before trial. In sum, don’t create a case against yourself by altering the medical records. 

Here, the falsification of records came to light during the deposition of the second nurse—who, being under oath, probably had little choice but to testify that the first nurse falsified the records. No doubt, this falsification made a bad case worse and gave the plaintiff leverage in securing more favorable settlement terms. 

You can’t make it right by rewriting history, but you can make it right by showing concern for the patient in your actions following a problem. You can also make it right by troubleshooting problems in a closed-door, formal peer review conference. Peer review conferences are designed for full and frank communication between clinicians and staff to solve problems, and as such they are protected from plaintiff disclosure.

This is an unfortunate case and a tragic loss of life. As clinicians, we must respect the potential life-ending power of parenteral narcotics. —DML

BOSTON – Treat to target in both early and established rheumatoid arthritis, recommended the authors of American College of Rheumatology draft guidelines on the management of RA.

The new ACR guidelines, expected to be finalized and published by the spring of 2015, also focus on the care of those patients whom most rheumatologists see in day-to-day practice, and they call for patience when trying a new therapy or new dose of an existing drug, Dr. Jasvinder Singh, of the division of clinical immunology and rheumatology at the University of Alabama, Birmingham, said to a standing-room-only crowd at the annual meeting of the American College of Rheumatology.

One of the guiding principles of the proposed recommendations is that “if a patient is doing well and the RA is under control, switching from one therapy to another should be done by a physician in consultation and agreement with the patient, and arbitrary switching between therapies should not be done,” he said.

Overall, the evidence-based guidelines emphasize several important aspects of RA care, including the following:

• Focus on the common patient and not exceptional cases.

• Give optimal doses of medications for 3 months before escalating or switching therapy.

• Assess disease activity using one of ACR’s recommended measures at a majority of encounters with RA patients.

• Consider methotrexate as the initial therapy in most RA patients.

• Methotrexate is the preferred monotherapy with a disease-modifying antirheumatic drug (DMARD), but other options include sulfasalazine, hydroxychloroquine, or leflunomide.

• A rheumatologist is the clinician of first choice for all patients with RA.

• Limit glucocorticoid treatment to the lowest possible dose for the shortest possible time to offer the best ratio of benefit to risk.

• Routinely assess patients’ functional status with standardized validated measures at least once yearly, or more frequently when RA is active.

The draft guidelines strongly recommend “using a treat-to-target strategy rather than a nontargeted approach” in both early and established RA.

Ideally, the target to be determined by the clinician and patient, should be remission or low disease activity. The guidelines acknowledge, however, that in some cases risk tolerance or comorbidities may require choice of a different and presumably less aggressive target.

Early RA

For early RA in treatment-naive patients, the guidelines offer an algorithm suggesting DMARD monotherapy for patients with low disease activity and, if the disease flares, recourse to short-term glucocorticoids.

For patients with moderately or highly active early RA, DMARD monotherapy can be followed with either short-term glucocorticoids, or in the case of DMARD failure, to either combination traditional DMARDs, a tumor necrosis factor inhibitor (TNFi) with or without methotrexate, or a non-TNF biologic agent with or without methotrexate, and with or without low-dose glucocorticoids. If the above therapies fail, the clinician and patient should consider a treatment course used for established RA.

Established RA

As with early RA, DMARD-naive patients with low disease activity may be started on DMARD monotherapy and proceed to traditional DMARD combinations, a TNFi with/without methotrexate, or non-TNF biologic with/without methotrexate, or tofacitinib with methotrexate. The guidelines offer a less robust recommendation about adding low-dose glucocorticoids, or short-term glucocorticoids for flares.

Patients who have not responded to treatment with single TNFi can move to a non-TNF biologic plus or minus methotrexate, or a different TNFi with/without methotrexate.

Patients who have not responded to treatment with multiple TNFi can try a non-TNF biologic plus/minus methotrexate, or tofacitinib with or without methotrexate.

Patients who have not responded to treatment with a single non-TNF biologic agent can try a different non-TNF biologic with/without methotrexate.

When both a TNFi and non-TNF biologic fail to help, the patient can try another non-TNF biologic plus/minus methotrexate, or tofacitinib plus/minus methotrexate.

Patients for whom multiple non-TNF biologic agents have failed can try either tofacitinib plus/minus methotrexate, or, if the patient is TNFi naive, a TNFi plus/minus methotrexate.

Special considerations

The guidelines make recommendations about treating patients with previously treated or untreated melanoma (TNFi preferable to tofacitinib) or nonmelanoma skin cancer (combination DMARD or non-TNF biologic preferable to TNFi) or a previously treated lymphoproliferative disorder (combination DMARD or non-TNF biologic such as abatacept, tocilizumab or rituximab over a TNFi). Patients with treated solid-organ malignancies, however, can be treated as other patients with RA are treated.

For patients with active hepatitis B or C virus infection who are receiving effective antiviral therapy, a DMARD, TNFi, non-TNF biologic, or tofacitinib can be prescribed, based on American Association for the Study of Liver Diseases case series and clinical experience, Dr. Singh said.

For patients with established RA and heart failure (HF), the guidelines recommend combination DMARD, non-TNF biologic, or tofacitinib over a TNFi, and if the patient has established or worsening HF on a TNFi, the three drug options above are preferable to switching the patient to another TNFi.

For patients with previous serious infections, however, there was less agreement on the optimal course. The guidelines, as currently planned, recommend a DMARD combination or abatacept over a TNFi in these patients, but there was no consensus about either rituximab or tocilizumab over a TNFi, Dr. Singh noted.

Tapering therapy

Finally, the proposed guidelines deal with therapeutic tapers. Specifically, for patients with established RA and low disease activity on maintenance methotrexate, the guidelines strongly recommend continuing on a traditional DMARD, TNFi, non-TNF biologic, or tofacitinib.

There is a conditional recommendation that patients with established RA in remission continuing on methotrexate can taper traditional DMARD therapy, TNFi, non-TNF biologic, or tofacitinib. But the guidelines strongly recommend against discontinuing all therapies in these patients, Dr. Singh emphasized.

“The strong recommendation is based on clinical experience that only a very small minority of patients are able to discontinue all therapies. Conditional recommendations here, supported by low-level evidence, are largely based upon expert opinion and clinical experience,” said Dr. Singh, who disclosed financial relationships with Allergan, Regeneron, Savient, and Takeda.

Join the queue

The proposed guidelines follow up on ACR’s 2012 guidelines, and will join an already crowded field of clinical practice recommendations, including those published in 2013 by the European League Against Rheumatism.

BOSTON – Treat to target in both early and established rheumatoid arthritis, recommended the authors of American College of Rheumatology draft guidelines on the management of RA.

The new ACR guidelines, expected to be finalized and published by the spring of 2015, also focus on the care of those patients whom most rheumatologists see in day-to-day practice, and they call for patience when trying a new therapy or new dose of an existing drug, Dr. Jasvinder Singh, of the division of clinical immunology and rheumatology at the University of Alabama, Birmingham, said to a standing-room-only crowd at the annual meeting of the American College of Rheumatology.

One of the guiding principles of the proposed recommendations is that “if a patient is doing well and the RA is under control, switching from one therapy to another should be done by a physician in consultation and agreement with the patient, and arbitrary switching between therapies should not be done,” he said.

Overall, the evidence-based guidelines emphasize several important aspects of RA care, including the following:

• Focus on the common patient and not exceptional cases.

• Give optimal doses of medications for 3 months before escalating or switching therapy.

• Assess disease activity using one of ACR’s recommended measures at a majority of encounters with RA patients.

• Consider methotrexate as the initial therapy in most RA patients.

• Methotrexate is the preferred monotherapy with a disease-modifying antirheumatic drug (DMARD), but other options include sulfasalazine, hydroxychloroquine, or leflunomide.

• A rheumatologist is the clinician of first choice for all patients with RA.

• Limit glucocorticoid treatment to the lowest possible dose for the shortest possible time to offer the best ratio of benefit to risk.

• Routinely assess patients’ functional status with standardized validated measures at least once yearly, or more frequently when RA is active.

The draft guidelines strongly recommend “using a treat-to-target strategy rather than a nontargeted approach” in both early and established RA.

Ideally, the target to be determined by the clinician and patient, should be remission or low disease activity. The guidelines acknowledge, however, that in some cases risk tolerance or comorbidities may require choice of a different and presumably less aggressive target.

Early RA

For early RA in treatment-naive patients, the guidelines offer an algorithm suggesting DMARD monotherapy for patients with low disease activity and, if the disease flares, recourse to short-term glucocorticoids.

For patients with moderately or highly active early RA, DMARD monotherapy can be followed with either short-term glucocorticoids, or in the case of DMARD failure, to either combination traditional DMARDs, a tumor necrosis factor inhibitor (TNFi) with or without methotrexate, or a non-TNF biologic agent with or without methotrexate, and with or without low-dose glucocorticoids. If the above therapies fail, the clinician and patient should consider a treatment course used for established RA.

Established RA

As with early RA, DMARD-naive patients with low disease activity may be started on DMARD monotherapy and proceed to traditional DMARD combinations, a TNFi with/without methotrexate, or non-TNF biologic with/without methotrexate, or tofacitinib with methotrexate. The guidelines offer a less robust recommendation about adding low-dose glucocorticoids, or short-term glucocorticoids for flares.

Patients who have not responded to treatment with single TNFi can move to a non-TNF biologic plus or minus methotrexate, or a different TNFi with/without methotrexate.

Patients who have not responded to treatment with multiple TNFi can try a non-TNF biologic plus/minus methotrexate, or tofacitinib with or without methotrexate.

Patients who have not responded to treatment with a single non-TNF biologic agent can try a different non-TNF biologic with/without methotrexate.

When both a TNFi and non-TNF biologic fail to help, the patient can try another non-TNF biologic plus/minus methotrexate, or tofacitinib plus/minus methotrexate.

Patients for whom multiple non-TNF biologic agents have failed can try either tofacitinib plus/minus methotrexate, or, if the patient is TNFi naive, a TNFi plus/minus methotrexate.

Special considerations

The guidelines make recommendations about treating patients with previously treated or untreated melanoma (TNFi preferable to tofacitinib) or nonmelanoma skin cancer (combination DMARD or non-TNF biologic preferable to TNFi) or a previously treated lymphoproliferative disorder (combination DMARD or non-TNF biologic such as abatacept, tocilizumab or rituximab over a TNFi). Patients with treated solid-organ malignancies, however, can be treated as other patients with RA are treated.

For patients with active hepatitis B or C virus infection who are receiving effective antiviral therapy, a DMARD, TNFi, non-TNF biologic, or tofacitinib can be prescribed, based on American Association for the Study of Liver Diseases case series and clinical experience, Dr. Singh said.

For patients with established RA and heart failure (HF), the guidelines recommend combination DMARD, non-TNF biologic, or tofacitinib over a TNFi, and if the patient has established or worsening HF on a TNFi, the three drug options above are preferable to switching the patient to another TNFi.

For patients with previous serious infections, however, there was less agreement on the optimal course. The guidelines, as currently planned, recommend a DMARD combination or abatacept over a TNFi in these patients, but there was no consensus about either rituximab or tocilizumab over a TNFi, Dr. Singh noted.

Tapering therapy

Finally, the proposed guidelines deal with therapeutic tapers. Specifically, for patients with established RA and low disease activity on maintenance methotrexate, the guidelines strongly recommend continuing on a traditional DMARD, TNFi, non-TNF biologic, or tofacitinib.

There is a conditional recommendation that patients with established RA in remission continuing on methotrexate can taper traditional DMARD therapy, TNFi, non-TNF biologic, or tofacitinib. But the guidelines strongly recommend against discontinuing all therapies in these patients, Dr. Singh emphasized.

“The strong recommendation is based on clinical experience that only a very small minority of patients are able to discontinue all therapies. Conditional recommendations here, supported by low-level evidence, are largely based upon expert opinion and clinical experience,” said Dr. Singh, who disclosed financial relationships with Allergan, Regeneron, Savient, and Takeda.

Join the queue

The proposed guidelines follow up on ACR’s 2012 guidelines, and will join an already crowded field of clinical practice recommendations, including those published in 2013 by the European League Against Rheumatism.

BOSTON – Treat to target in both early and established rheumatoid arthritis, recommended the authors of American College of Rheumatology draft guidelines on the management of RA.

The new ACR guidelines, expected to be finalized and published by the spring of 2015, also focus on the care of those patients whom most rheumatologists see in day-to-day practice, and they call for patience when trying a new therapy or new dose of an existing drug, Dr. Jasvinder Singh, of the division of clinical immunology and rheumatology at the University of Alabama, Birmingham, said to a standing-room-only crowd at the annual meeting of the American College of Rheumatology.

One of the guiding principles of the proposed recommendations is that “if a patient is doing well and the RA is under control, switching from one therapy to another should be done by a physician in consultation and agreement with the patient, and arbitrary switching between therapies should not be done,” he said.

Overall, the evidence-based guidelines emphasize several important aspects of RA care, including the following:

• Focus on the common patient and not exceptional cases.

• Give optimal doses of medications for 3 months before escalating or switching therapy.

• Assess disease activity using one of ACR’s recommended measures at a majority of encounters with RA patients.

• Consider methotrexate as the initial therapy in most RA patients.

• Methotrexate is the preferred monotherapy with a disease-modifying antirheumatic drug (DMARD), but other options include sulfasalazine, hydroxychloroquine, or leflunomide.

• A rheumatologist is the clinician of first choice for all patients with RA.

• Limit glucocorticoid treatment to the lowest possible dose for the shortest possible time to offer the best ratio of benefit to risk.

• Routinely assess patients’ functional status with standardized validated measures at least once yearly, or more frequently when RA is active.

The draft guidelines strongly recommend “using a treat-to-target strategy rather than a nontargeted approach” in both early and established RA.

Ideally, the target to be determined by the clinician and patient, should be remission or low disease activity. The guidelines acknowledge, however, that in some cases risk tolerance or comorbidities may require choice of a different and presumably less aggressive target.

Early RA

For early RA in treatment-naive patients, the guidelines offer an algorithm suggesting DMARD monotherapy for patients with low disease activity and, if the disease flares, recourse to short-term glucocorticoids.

For patients with moderately or highly active early RA, DMARD monotherapy can be followed with either short-term glucocorticoids, or in the case of DMARD failure, to either combination traditional DMARDs, a tumor necrosis factor inhibitor (TNFi) with or without methotrexate, or a non-TNF biologic agent with or without methotrexate, and with or without low-dose glucocorticoids. If the above therapies fail, the clinician and patient should consider a treatment course used for established RA.

Established RA

As with early RA, DMARD-naive patients with low disease activity may be started on DMARD monotherapy and proceed to traditional DMARD combinations, a TNFi with/without methotrexate, or non-TNF biologic with/without methotrexate, or tofacitinib with methotrexate. The guidelines offer a less robust recommendation about adding low-dose glucocorticoids, or short-term glucocorticoids for flares.

Patients who have not responded to treatment with single TNFi can move to a non-TNF biologic plus or minus methotrexate, or a different TNFi with/without methotrexate.

Patients who have not responded to treatment with multiple TNFi can try a non-TNF biologic plus/minus methotrexate, or tofacitinib with or without methotrexate.

Patients who have not responded to treatment with a single non-TNF biologic agent can try a different non-TNF biologic with/without methotrexate.

When both a TNFi and non-TNF biologic fail to help, the patient can try another non-TNF biologic plus/minus methotrexate, or tofacitinib plus/minus methotrexate.

Patients for whom multiple non-TNF biologic agents have failed can try either tofacitinib plus/minus methotrexate, or, if the patient is TNFi naive, a TNFi plus/minus methotrexate.

Special considerations

The guidelines make recommendations about treating patients with previously treated or untreated melanoma (TNFi preferable to tofacitinib) or nonmelanoma skin cancer (combination DMARD or non-TNF biologic preferable to TNFi) or a previously treated lymphoproliferative disorder (combination DMARD or non-TNF biologic such as abatacept, tocilizumab or rituximab over a TNFi). Patients with treated solid-organ malignancies, however, can be treated as other patients with RA are treated.

For patients with active hepatitis B or C virus infection who are receiving effective antiviral therapy, a DMARD, TNFi, non-TNF biologic, or tofacitinib can be prescribed, based on American Association for the Study of Liver Diseases case series and clinical experience, Dr. Singh said.

For patients with established RA and heart failure (HF), the guidelines recommend combination DMARD, non-TNF biologic, or tofacitinib over a TNFi, and if the patient has established or worsening HF on a TNFi, the three drug options above are preferable to switching the patient to another TNFi.

For patients with previous serious infections, however, there was less agreement on the optimal course. The guidelines, as currently planned, recommend a DMARD combination or abatacept over a TNFi in these patients, but there was no consensus about either rituximab or tocilizumab over a TNFi, Dr. Singh noted.

Tapering therapy

Finally, the proposed guidelines deal with therapeutic tapers. Specifically, for patients with established RA and low disease activity on maintenance methotrexate, the guidelines strongly recommend continuing on a traditional DMARD, TNFi, non-TNF biologic, or tofacitinib.

There is a conditional recommendation that patients with established RA in remission continuing on methotrexate can taper traditional DMARD therapy, TNFi, non-TNF biologic, or tofacitinib. But the guidelines strongly recommend against discontinuing all therapies in these patients, Dr. Singh emphasized.

“The strong recommendation is based on clinical experience that only a very small minority of patients are able to discontinue all therapies. Conditional recommendations here, supported by low-level evidence, are largely based upon expert opinion and clinical experience,” said Dr. Singh, who disclosed financial relationships with Allergan, Regeneron, Savient, and Takeda.

Join the queue

The proposed guidelines follow up on ACR’s 2012 guidelines, and will join an already crowded field of clinical practice recommendations, including those published in 2013 by the European League Against Rheumatism.