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Group creates guide for PICC use
A group of international experts has created a guide to promote the appropriate use of peripherally inserted central catheters (PICCs) in adults.
The guide, called Michigan Appropriateness Guide for Intravenous Catheters (MAGIC), was published in Annals of Internal Medicine.
MAGIC is based on a review of evidence and was designed to give clinicians an easy-to-use framework to pick the right venous access device for each patient.
“PICCs, or peripherally inserted central catheters, have become especially convenient to place, and their use has gone up dramatically, as have the complications from them,” said guideline author Vineet Chopra, MD, of the University of Michigan in Ann Arbor.
“The easiest way to prevent these complications is not to place a PICC in the first place. So we set out to determine when the use of a PICC is appropriate and when other choices are the best.”
The experts reviewed 665 scenarios in which PICCs were used. Their use was deemed appropriate in 38% (n=253) of cases and inappropriate in 43% (n=288). In 19% (n=124) of cases, the experts could not agree or were unsure about whether PICC use was appropriate.
The experts said that, in patients with cancer, PICCs are appropriate for irritant or vesicant infusion, regardless of the duration of use.
On the other hand, they said PICC use is inappropriate for peripherally compatible infusions when the proposed duration of use is 5 days or fewer. And when the duration is between 6 days and 14 days, midline and ultrasonography-guided peripheral intravenous catheters should be used over PICCs.
The experts also said that nontunneled central venous catheters should be used over PICCs in critically ill patients when the duration of use is likely to be 14 days or fewer.
How MAGIC happened
The panel of 15 experts included doctors and nurses from a range of fields where PICCs and other such devices are commonly used, such as vascular nursing, critical care, infectious disease, and oncology. Also participating was a patient who had suffered complications from various intravenous devices and still lives with the consequences.
The panel evaluated the scenarios and supporting medical literature, and made its recommendations, using the RAND/UCLA Appropriateness Method.
The panel did not consider pediatric use of PICCs and other vascular access devices, but they hope their work could provide a framework for a similar effort in pediatrics.
Putting MAGIC to the test
MAGIC is getting its first test in 47 Michigan hospitals taking part in a patient safety project known as the Michigan Hospital Medicine Safety Consortium.
Researchers also plan to test ways to deploy MAGIC across the Veterans Affairs health system, working with the VA National Center for Patient Safety and the No Preventable Harms Campaign.
Even as they evaluate MAGIC’s ability to improve appropriate use of different devices and reduce complications, the team behind the new guide hopes other clinicians will begin using it.
“IV devices of all kinds are being put into patients without much thought about risks, benefits, or alternatives,” Dr Chopra said. “At the end of the day, we hope MAGIC will give providers the information they need to make a good decision for their patient, one that will render these devices appropriate and safe.”
Dr Chopra and his colleagues have also launched a website, improvepicc.com, that provides links to research on PICCs and other resources for clinicians. 
A group of international experts has created a guide to promote the appropriate use of peripherally inserted central catheters (PICCs) in adults.
The guide, called Michigan Appropriateness Guide for Intravenous Catheters (MAGIC), was published in Annals of Internal Medicine.
MAGIC is based on a review of evidence and was designed to give clinicians an easy-to-use framework to pick the right venous access device for each patient.
“PICCs, or peripherally inserted central catheters, have become especially convenient to place, and their use has gone up dramatically, as have the complications from them,” said guideline author Vineet Chopra, MD, of the University of Michigan in Ann Arbor.
“The easiest way to prevent these complications is not to place a PICC in the first place. So we set out to determine when the use of a PICC is appropriate and when other choices are the best.”
The experts reviewed 665 scenarios in which PICCs were used. Their use was deemed appropriate in 38% (n=253) of cases and inappropriate in 43% (n=288). In 19% (n=124) of cases, the experts could not agree or were unsure about whether PICC use was appropriate.
The experts said that, in patients with cancer, PICCs are appropriate for irritant or vesicant infusion, regardless of the duration of use.
On the other hand, they said PICC use is inappropriate for peripherally compatible infusions when the proposed duration of use is 5 days or fewer. And when the duration is between 6 days and 14 days, midline and ultrasonography-guided peripheral intravenous catheters should be used over PICCs.
The experts also said that nontunneled central venous catheters should be used over PICCs in critically ill patients when the duration of use is likely to be 14 days or fewer.
How MAGIC happened
The panel of 15 experts included doctors and nurses from a range of fields where PICCs and other such devices are commonly used, such as vascular nursing, critical care, infectious disease, and oncology. Also participating was a patient who had suffered complications from various intravenous devices and still lives with the consequences.
The panel evaluated the scenarios and supporting medical literature, and made its recommendations, using the RAND/UCLA Appropriateness Method.
The panel did not consider pediatric use of PICCs and other vascular access devices, but they hope their work could provide a framework for a similar effort in pediatrics.
Putting MAGIC to the test
MAGIC is getting its first test in 47 Michigan hospitals taking part in a patient safety project known as the Michigan Hospital Medicine Safety Consortium.
Researchers also plan to test ways to deploy MAGIC across the Veterans Affairs health system, working with the VA National Center for Patient Safety and the No Preventable Harms Campaign.
Even as they evaluate MAGIC’s ability to improve appropriate use of different devices and reduce complications, the team behind the new guide hopes other clinicians will begin using it.
“IV devices of all kinds are being put into patients without much thought about risks, benefits, or alternatives,” Dr Chopra said. “At the end of the day, we hope MAGIC will give providers the information they need to make a good decision for their patient, one that will render these devices appropriate and safe.”
Dr Chopra and his colleagues have also launched a website, improvepicc.com, that provides links to research on PICCs and other resources for clinicians.
A group of international experts has created a guide to promote the appropriate use of peripherally inserted central catheters (PICCs) in adults.
The guide, called Michigan Appropriateness Guide for Intravenous Catheters (MAGIC), was published in Annals of Internal Medicine.
MAGIC is based on a review of evidence and was designed to give clinicians an easy-to-use framework to pick the right venous access device for each patient.
“PICCs, or peripherally inserted central catheters, have become especially convenient to place, and their use has gone up dramatically, as have the complications from them,” said guideline author Vineet Chopra, MD, of the University of Michigan in Ann Arbor.
“The easiest way to prevent these complications is not to place a PICC in the first place. So we set out to determine when the use of a PICC is appropriate and when other choices are the best.”
The experts reviewed 665 scenarios in which PICCs were used. Their use was deemed appropriate in 38% (n=253) of cases and inappropriate in 43% (n=288). In 19% (n=124) of cases, the experts could not agree or were unsure about whether PICC use was appropriate.
The experts said that, in patients with cancer, PICCs are appropriate for irritant or vesicant infusion, regardless of the duration of use.
On the other hand, they said PICC use is inappropriate for peripherally compatible infusions when the proposed duration of use is 5 days or fewer. And when the duration is between 6 days and 14 days, midline and ultrasonography-guided peripheral intravenous catheters should be used over PICCs.
The experts also said that nontunneled central venous catheters should be used over PICCs in critically ill patients when the duration of use is likely to be 14 days or fewer.
How MAGIC happened
The panel of 15 experts included doctors and nurses from a range of fields where PICCs and other such devices are commonly used, such as vascular nursing, critical care, infectious disease, and oncology. Also participating was a patient who had suffered complications from various intravenous devices and still lives with the consequences.
The panel evaluated the scenarios and supporting medical literature, and made its recommendations, using the RAND/UCLA Appropriateness Method.
The panel did not consider pediatric use of PICCs and other vascular access devices, but they hope their work could provide a framework for a similar effort in pediatrics.
Putting MAGIC to the test
MAGIC is getting its first test in 47 Michigan hospitals taking part in a patient safety project known as the Michigan Hospital Medicine Safety Consortium.
Researchers also plan to test ways to deploy MAGIC across the Veterans Affairs health system, working with the VA National Center for Patient Safety and the No Preventable Harms Campaign.
Even as they evaluate MAGIC’s ability to improve appropriate use of different devices and reduce complications, the team behind the new guide hopes other clinicians will begin using it.
“IV devices of all kinds are being put into patients without much thought about risks, benefits, or alternatives,” Dr Chopra said. “At the end of the day, we hope MAGIC will give providers the information they need to make a good decision for their patient, one that will render these devices appropriate and safe.”
Dr Chopra and his colleagues have also launched a website, improvepicc.com, that provides links to research on PICCs and other resources for clinicians.
Scientists describe new way to create etoposide
Scientists have reported a new way to produce the chemotherapeutic agent etoposide, and they believe this discovery could lead to a more stable supply of the drug.
Currently, producing etoposide requires isolating one of its precursors, (–)-podophyllotoxin, from the endangered, slow-growing, Himalayan Mayapple plant (Podophyllum hexandrum).
But researchers found they could generate the immediate precursor to etoposide—(–)-4’-desmethyl-epipodophyllotoxin—in a more easily accessible, faster-growing tobacco plant (Nicotiana benthamiana).
Elizabeth Sattely, PhD, of Stanford University in California, and her graduate student, Warren Lau, described this work in Science.
The pair noted that there are 4 known genes behind (–)-podophyllotoxin production, but the full recipe for this compound has eluded researchers, in part because of the Mayapple’s immense genome.
To tap into the Mayapple’s chemotherapeutic potential, Lau and Dr Sattely first focused on the 4 known genes—PLR, SDH, CYP719A23, and DIR. Then, they analyzed RNA sequencing data from the Mayapple to identify similar genes.
Next, the pair manipulated the tobacco plant to express multiple gene candidates at once and identified the resulting compounds in leaf tissue using mass spectrometry.
Dr Sattely and Lau identified 6 new genes—OMT3, CYP71CU1, OMT1, 2-ODD, CYP71BE54, and CYP82D61.
These genes, when expressed with the original 4, produce the immediate etoposide precursor (–)-4′-desmethyl-epipodophyllotoxin, which outperforms (–)-podophyllotoxin as a chemotherapy ingredient.
The researchers said this work has revealed a simpler and more direct route to etoposide that circumvents the semisynthetic epimerization and demethylation required to produce etoposide from (–)-podophyllotoxin.
However, Dr Sattely said the eventual goal is to use yeast instead of plants to produce etoposide. Yeast can be grown in large vats and may therefore provide a more stable source of drugs.
In addition, yeast provides the opportunity to modify genes to produce proteins with slightly different functions. And it may be possible to feed the yeast a slightly different starting product, thereby changing the chemical a molecular assembly line churns out.
These approaches could provide a way of tweaking existing drugs in an effort to improve them.
Scientists have reported a new way to produce the chemotherapeutic agent etoposide, and they believe this discovery could lead to a more stable supply of the drug.
Currently, producing etoposide requires isolating one of its precursors, (–)-podophyllotoxin, from the endangered, slow-growing, Himalayan Mayapple plant (Podophyllum hexandrum).
But researchers found they could generate the immediate precursor to etoposide—(–)-4’-desmethyl-epipodophyllotoxin—in a more easily accessible, faster-growing tobacco plant (Nicotiana benthamiana).
Elizabeth Sattely, PhD, of Stanford University in California, and her graduate student, Warren Lau, described this work in Science.
The pair noted that there are 4 known genes behind (–)-podophyllotoxin production, but the full recipe for this compound has eluded researchers, in part because of the Mayapple’s immense genome.
To tap into the Mayapple’s chemotherapeutic potential, Lau and Dr Sattely first focused on the 4 known genes—PLR, SDH, CYP719A23, and DIR. Then, they analyzed RNA sequencing data from the Mayapple to identify similar genes.
Next, the pair manipulated the tobacco plant to express multiple gene candidates at once and identified the resulting compounds in leaf tissue using mass spectrometry.
Dr Sattely and Lau identified 6 new genes—OMT3, CYP71CU1, OMT1, 2-ODD, CYP71BE54, and CYP82D61.
These genes, when expressed with the original 4, produce the immediate etoposide precursor (–)-4′-desmethyl-epipodophyllotoxin, which outperforms (–)-podophyllotoxin as a chemotherapy ingredient.
The researchers said this work has revealed a simpler and more direct route to etoposide that circumvents the semisynthetic epimerization and demethylation required to produce etoposide from (–)-podophyllotoxin.
However, Dr Sattely said the eventual goal is to use yeast instead of plants to produce etoposide. Yeast can be grown in large vats and may therefore provide a more stable source of drugs.
In addition, yeast provides the opportunity to modify genes to produce proteins with slightly different functions. And it may be possible to feed the yeast a slightly different starting product, thereby changing the chemical a molecular assembly line churns out.
These approaches could provide a way of tweaking existing drugs in an effort to improve them.
Scientists have reported a new way to produce the chemotherapeutic agent etoposide, and they believe this discovery could lead to a more stable supply of the drug.
Currently, producing etoposide requires isolating one of its precursors, (–)-podophyllotoxin, from the endangered, slow-growing, Himalayan Mayapple plant (Podophyllum hexandrum).
But researchers found they could generate the immediate precursor to etoposide—(–)-4’-desmethyl-epipodophyllotoxin—in a more easily accessible, faster-growing tobacco plant (Nicotiana benthamiana).
Elizabeth Sattely, PhD, of Stanford University in California, and her graduate student, Warren Lau, described this work in Science.
The pair noted that there are 4 known genes behind (–)-podophyllotoxin production, but the full recipe for this compound has eluded researchers, in part because of the Mayapple’s immense genome.
To tap into the Mayapple’s chemotherapeutic potential, Lau and Dr Sattely first focused on the 4 known genes—PLR, SDH, CYP719A23, and DIR. Then, they analyzed RNA sequencing data from the Mayapple to identify similar genes.
Next, the pair manipulated the tobacco plant to express multiple gene candidates at once and identified the resulting compounds in leaf tissue using mass spectrometry.
Dr Sattely and Lau identified 6 new genes—OMT3, CYP71CU1, OMT1, 2-ODD, CYP71BE54, and CYP82D61.
These genes, when expressed with the original 4, produce the immediate etoposide precursor (–)-4′-desmethyl-epipodophyllotoxin, which outperforms (–)-podophyllotoxin as a chemotherapy ingredient.
The researchers said this work has revealed a simpler and more direct route to etoposide that circumvents the semisynthetic epimerization and demethylation required to produce etoposide from (–)-podophyllotoxin.
However, Dr Sattely said the eventual goal is to use yeast instead of plants to produce etoposide. Yeast can be grown in large vats and may therefore provide a more stable source of drugs.
In addition, yeast provides the opportunity to modify genes to produce proteins with slightly different functions. And it may be possible to feed the yeast a slightly different starting product, thereby changing the chemical a molecular assembly line churns out.
These approaches could provide a way of tweaking existing drugs in an effort to improve them.
Online tool may aid study of immune system
Photo by Darren Baker
Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.
The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.
Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.
“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.
“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”
ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.
“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.
“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”
Photo by Darren Baker
Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.
The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.
Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.
“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.
“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”
ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.
“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.
“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”
Photo by Darren Baker
Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.
The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.
Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.
“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.
“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”
ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.
“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.
“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”
Model may aid cancer drug discovery
Photo by Darren Baker
Researchers say they have created a model that can show how nearly any drug behaves in P-glycoprotein (P-gp), a protein associated with chemotherapy failure.
The team developed this computer-generated model to overcome the problem of relying on static images for the structure of P-gp.
When the researchers introduced drugs into the model, the drugs responded the way they do in real life and behaved according to predictions.
John G. Wise, PhD, of Southern Methodist University in Dallas, Texas, and his colleagues described the model in Biochemistry.
“The value of this fundamental research is that it generates dynamic mechanisms that let us understand something in biochemistry, in biology,” Dr Wise said. “And by understanding P-gp in such detail, we can now think of ways to better and more specifically inhibit it.”
Dr Wise and his colleagues noted that P-gp protects cells by pumping out toxins, but that can include chemotherapy drugs. So inhibiting P-gp’s pumping action might circumvent chemotherapy failure.
With than in mind, the team tested tariquidar, a P-gp inhibitor in clinical trials, in their model.
It hasn’t been clear exactly where tariquidar binds in P-gp. But the model showed the drug prefers to bind high in the protein. Tariquidar also behaved as expected. It wasn’t effectively pumped from the cell.
“Now we have more details on how tariquidar inhibits P-gp, where it inhibits, and what it’s actually binding to,” Dr Wise said.
He and his colleagues also used their model to uncover additional details about the behavior of other drugs in P-gp.
“For a long time, it’s been thought that there are at least a couple of distinct binding sites for drugs,” Dr Wise said.
“Sure enough, with our models, we found that [the chemotherapeutic agent] daunorubicin, at least, prefers to bind on one side of the P-gp model, while verapamil—a commonly prescribed blood pressure medicine—prefers the other side.”
Not only did the researchers show computationally that there are 2 different starting points for drugs, they also showed that there are 2 different pathways to get the drugs through.
“The 2 different drugs start at different sites, and they’re funneled to the outside by being pushed by the protein,” Dr Wise said. “But the actual parts of the protein that are pushing the drugs out are different.”
Drug discovery
Being able to watch molecular machinery up close, while it is doing its job the way it does in real life, may spark new drug discoveries to fight cancer, Dr Wise said.
“Having an accurate model that actually moves—that shows the dynamics of the thing—is incredibly helpful in developing therapies against a molecular target to inhibit it,” Dr Wise said. “The only other ways to do it are blind, and the chances of success using blind methods are very low.”
“Scientists have tried for 30 years to find inhibitors of this pump and have done it without knowing the structure and with only little knowledge about the mechanism, screening more or less blindly for compounds that inhibit the thing.”
“They found drugs that worked in the test tube and that worked in cultured cells but that didn’t work in the patient. With our model, because we can see the pump moving, we can probably predict better what’s going to make an inhibitor actually work well.”
Dr Wise and his colleagues used the P-gp model to virtually screen millions of publicly available compounds. They discovered 3 new drug leads that could ultimately inhibit P-gp and offer better odds of survival to prostate cancer patients.
The researchers reported these findings in Pharmacology Research & Perspectives.
Creating the model
To build the P-gp model, Dr Wise and his colleagues used static structures from the US Protein Data Bank repository. They used structures showing various stages of transport to simulate 4 points of reference.
From there, the team fed a supercomputer parameters and characteristics of the protein, as well as how it should behave physically, including when kinetic energy was added to bring the protein and its surrounding membrane and water up to body temperature.
The animated model resulted from calculating differences between 2 structures and using targeted molecular dynamics programs to slightly nudge the model to the next step.
“You do that several million times and make several trillion calculations, and you arrive at the next structure,” Dr Wise said. “In this way, we can nudge P-gp through a full catalytic transport cycle.”
Finally, using a docking program, the researchers individually introduced daunorubicin and other drugs into the protein and watched the drugs move through P-gp’s catalytic cycle.
“What happened was: the drugs moved,” Dr Wise said. “And they moved the way they should move, clinically, biochemically, physiologically, to pump the compounds out of the cell.”
Challenging the model
The researchers ran a critical control to further test if the model worked.
“We thought maybe anything you put in the protein, relevant or not, would get pumped through,” Dr Wise said. “So we put in something that is not a transport substrate of P-gp, something that, biochemically, would never be transported by P-gp.”
“We put it in, starting where daunorubicin is effectively pumped out, and, very quickly, the compound left the protein. But it left the opposite way, back into the cell. This experiment gave us more confidence that what we are seeing in these models is reflecting what happens in the cell.”
Dr Wise admitted that, until he saw it for himself, he had doubts the virtual P-gp model would behave like real-life P-gp.
“It’s a crude approximation of a complex, sophisticated human protein, but it’s so much better than the static images available now,” Dr Wise said.
“I’ve got to emphasize for all the disbelievers, for the ‘culture of doubters’ out there, that this model works. It moves the drugs through the membrane. That speaks for itself. What P-gp does in the cell, cancerous or normal, it does in our simulations.”
Photo by Darren Baker
Researchers say they have created a model that can show how nearly any drug behaves in P-glycoprotein (P-gp), a protein associated with chemotherapy failure.
The team developed this computer-generated model to overcome the problem of relying on static images for the structure of P-gp.
When the researchers introduced drugs into the model, the drugs responded the way they do in real life and behaved according to predictions.
John G. Wise, PhD, of Southern Methodist University in Dallas, Texas, and his colleagues described the model in Biochemistry.
“The value of this fundamental research is that it generates dynamic mechanisms that let us understand something in biochemistry, in biology,” Dr Wise said. “And by understanding P-gp in such detail, we can now think of ways to better and more specifically inhibit it.”
Dr Wise and his colleagues noted that P-gp protects cells by pumping out toxins, but that can include chemotherapy drugs. So inhibiting P-gp’s pumping action might circumvent chemotherapy failure.
With than in mind, the team tested tariquidar, a P-gp inhibitor in clinical trials, in their model.
It hasn’t been clear exactly where tariquidar binds in P-gp. But the model showed the drug prefers to bind high in the protein. Tariquidar also behaved as expected. It wasn’t effectively pumped from the cell.
“Now we have more details on how tariquidar inhibits P-gp, where it inhibits, and what it’s actually binding to,” Dr Wise said.
He and his colleagues also used their model to uncover additional details about the behavior of other drugs in P-gp.
“For a long time, it’s been thought that there are at least a couple of distinct binding sites for drugs,” Dr Wise said.
“Sure enough, with our models, we found that [the chemotherapeutic agent] daunorubicin, at least, prefers to bind on one side of the P-gp model, while verapamil—a commonly prescribed blood pressure medicine—prefers the other side.”
Not only did the researchers show computationally that there are 2 different starting points for drugs, they also showed that there are 2 different pathways to get the drugs through.
“The 2 different drugs start at different sites, and they’re funneled to the outside by being pushed by the protein,” Dr Wise said. “But the actual parts of the protein that are pushing the drugs out are different.”
Drug discovery
Being able to watch molecular machinery up close, while it is doing its job the way it does in real life, may spark new drug discoveries to fight cancer, Dr Wise said.
“Having an accurate model that actually moves—that shows the dynamics of the thing—is incredibly helpful in developing therapies against a molecular target to inhibit it,” Dr Wise said. “The only other ways to do it are blind, and the chances of success using blind methods are very low.”
“Scientists have tried for 30 years to find inhibitors of this pump and have done it without knowing the structure and with only little knowledge about the mechanism, screening more or less blindly for compounds that inhibit the thing.”
“They found drugs that worked in the test tube and that worked in cultured cells but that didn’t work in the patient. With our model, because we can see the pump moving, we can probably predict better what’s going to make an inhibitor actually work well.”
Dr Wise and his colleagues used the P-gp model to virtually screen millions of publicly available compounds. They discovered 3 new drug leads that could ultimately inhibit P-gp and offer better odds of survival to prostate cancer patients.
The researchers reported these findings in Pharmacology Research & Perspectives.
Creating the model
To build the P-gp model, Dr Wise and his colleagues used static structures from the US Protein Data Bank repository. They used structures showing various stages of transport to simulate 4 points of reference.
From there, the team fed a supercomputer parameters and characteristics of the protein, as well as how it should behave physically, including when kinetic energy was added to bring the protein and its surrounding membrane and water up to body temperature.
The animated model resulted from calculating differences between 2 structures and using targeted molecular dynamics programs to slightly nudge the model to the next step.
“You do that several million times and make several trillion calculations, and you arrive at the next structure,” Dr Wise said. “In this way, we can nudge P-gp through a full catalytic transport cycle.”
Finally, using a docking program, the researchers individually introduced daunorubicin and other drugs into the protein and watched the drugs move through P-gp’s catalytic cycle.
“What happened was: the drugs moved,” Dr Wise said. “And they moved the way they should move, clinically, biochemically, physiologically, to pump the compounds out of the cell.”
Challenging the model
The researchers ran a critical control to further test if the model worked.
“We thought maybe anything you put in the protein, relevant or not, would get pumped through,” Dr Wise said. “So we put in something that is not a transport substrate of P-gp, something that, biochemically, would never be transported by P-gp.”
“We put it in, starting where daunorubicin is effectively pumped out, and, very quickly, the compound left the protein. But it left the opposite way, back into the cell. This experiment gave us more confidence that what we are seeing in these models is reflecting what happens in the cell.”
Dr Wise admitted that, until he saw it for himself, he had doubts the virtual P-gp model would behave like real-life P-gp.
“It’s a crude approximation of a complex, sophisticated human protein, but it’s so much better than the static images available now,” Dr Wise said.
“I’ve got to emphasize for all the disbelievers, for the ‘culture of doubters’ out there, that this model works. It moves the drugs through the membrane. That speaks for itself. What P-gp does in the cell, cancerous or normal, it does in our simulations.”
Photo by Darren Baker
Researchers say they have created a model that can show how nearly any drug behaves in P-glycoprotein (P-gp), a protein associated with chemotherapy failure.
The team developed this computer-generated model to overcome the problem of relying on static images for the structure of P-gp.
When the researchers introduced drugs into the model, the drugs responded the way they do in real life and behaved according to predictions.
John G. Wise, PhD, of Southern Methodist University in Dallas, Texas, and his colleagues described the model in Biochemistry.
“The value of this fundamental research is that it generates dynamic mechanisms that let us understand something in biochemistry, in biology,” Dr Wise said. “And by understanding P-gp in such detail, we can now think of ways to better and more specifically inhibit it.”
Dr Wise and his colleagues noted that P-gp protects cells by pumping out toxins, but that can include chemotherapy drugs. So inhibiting P-gp’s pumping action might circumvent chemotherapy failure.
With than in mind, the team tested tariquidar, a P-gp inhibitor in clinical trials, in their model.
It hasn’t been clear exactly where tariquidar binds in P-gp. But the model showed the drug prefers to bind high in the protein. Tariquidar also behaved as expected. It wasn’t effectively pumped from the cell.
“Now we have more details on how tariquidar inhibits P-gp, where it inhibits, and what it’s actually binding to,” Dr Wise said.
He and his colleagues also used their model to uncover additional details about the behavior of other drugs in P-gp.
“For a long time, it’s been thought that there are at least a couple of distinct binding sites for drugs,” Dr Wise said.
“Sure enough, with our models, we found that [the chemotherapeutic agent] daunorubicin, at least, prefers to bind on one side of the P-gp model, while verapamil—a commonly prescribed blood pressure medicine—prefers the other side.”
Not only did the researchers show computationally that there are 2 different starting points for drugs, they also showed that there are 2 different pathways to get the drugs through.
“The 2 different drugs start at different sites, and they’re funneled to the outside by being pushed by the protein,” Dr Wise said. “But the actual parts of the protein that are pushing the drugs out are different.”
Drug discovery
Being able to watch molecular machinery up close, while it is doing its job the way it does in real life, may spark new drug discoveries to fight cancer, Dr Wise said.
“Having an accurate model that actually moves—that shows the dynamics of the thing—is incredibly helpful in developing therapies against a molecular target to inhibit it,” Dr Wise said. “The only other ways to do it are blind, and the chances of success using blind methods are very low.”
“Scientists have tried for 30 years to find inhibitors of this pump and have done it without knowing the structure and with only little knowledge about the mechanism, screening more or less blindly for compounds that inhibit the thing.”
“They found drugs that worked in the test tube and that worked in cultured cells but that didn’t work in the patient. With our model, because we can see the pump moving, we can probably predict better what’s going to make an inhibitor actually work well.”
Dr Wise and his colleagues used the P-gp model to virtually screen millions of publicly available compounds. They discovered 3 new drug leads that could ultimately inhibit P-gp and offer better odds of survival to prostate cancer patients.
The researchers reported these findings in Pharmacology Research & Perspectives.
Creating the model
To build the P-gp model, Dr Wise and his colleagues used static structures from the US Protein Data Bank repository. They used structures showing various stages of transport to simulate 4 points of reference.
From there, the team fed a supercomputer parameters and characteristics of the protein, as well as how it should behave physically, including when kinetic energy was added to bring the protein and its surrounding membrane and water up to body temperature.
The animated model resulted from calculating differences between 2 structures and using targeted molecular dynamics programs to slightly nudge the model to the next step.
“You do that several million times and make several trillion calculations, and you arrive at the next structure,” Dr Wise said. “In this way, we can nudge P-gp through a full catalytic transport cycle.”
Finally, using a docking program, the researchers individually introduced daunorubicin and other drugs into the protein and watched the drugs move through P-gp’s catalytic cycle.
“What happened was: the drugs moved,” Dr Wise said. “And they moved the way they should move, clinically, biochemically, physiologically, to pump the compounds out of the cell.”
Challenging the model
The researchers ran a critical control to further test if the model worked.
“We thought maybe anything you put in the protein, relevant or not, would get pumped through,” Dr Wise said. “So we put in something that is not a transport substrate of P-gp, something that, biochemically, would never be transported by P-gp.”
“We put it in, starting where daunorubicin is effectively pumped out, and, very quickly, the compound left the protein. But it left the opposite way, back into the cell. This experiment gave us more confidence that what we are seeing in these models is reflecting what happens in the cell.”
Dr Wise admitted that, until he saw it for himself, he had doubts the virtual P-gp model would behave like real-life P-gp.
“It’s a crude approximation of a complex, sophisticated human protein, but it’s so much better than the static images available now,” Dr Wise said.
“I’ve got to emphasize for all the disbelievers, for the ‘culture of doubters’ out there, that this model works. It moves the drugs through the membrane. That speaks for itself. What P-gp does in the cell, cancerous or normal, it does in our simulations.”
Iron supplements don’t increase malaria risk
Photo by Nina Matthews
Taking iron supplements during pregnancy does not increase a woman’s risk of contracting malaria, according to research published in JAMA.
Investigators studied nearly 500 pregnant women in a malaria-endemic region, comparing those who received daily iron supplements to those who received placebo.
Roughly half of the women in each group developed malaria, and iron supplementation was associated with benefits for mothers and children.
Martin N. Mwangi, PhD, of Wageningen University in The Netherlands, and his colleagues conducted this research.
The team said current estimates suggest that anemia affects 57% of pregnant women in Africa. And although iron deficiency is the most common cause, iron supplementation during pregnancy has uncertain health benefits.
There is some evidence to suggest that iron supplementation may increase the risk of infectious diseases, including malaria.
To investigate this association, Dr Mwangi and his colleagues studied 470 pregnant women living in a malaria-endemic area in Kenya. The subjects were randomized to daily supplementation with 60 mg of iron (n=237) or placebo (n=233) until 1 month postpartum.
All women received 5.7 mg iron per day through flour fortification during the intervention, as well as the usual intermittent preventive treatment against malaria.
Among the 470 participating women, 40 women (22 in the iron group and 18 in the placebo group) were lost to follow-up or excluded at birth. Twelve mothers were lost to follow-up postpartum (5 iron, 7 placebo). At study entry, 190 of 318 women (60%) were iron-deficient.
After childbirth, there was no significant difference in Plasmodium infection between the treatment groups. Infection occurred in 50.9% of women in the iron group and 52.1% in the placebo group (P=0.83).
There was a significant increase in hemoglobin concentration and a significant decrease in anemia among mothers who received iron (P<0.001 for both). Mothers in the iron group also had a significantly lower mean zinc protoporphyrin (ZPP)-heme ratio in whole blood (P<0.001) and erythrocytes (P<0.001).
Children born to mothers in the iron group had a significantly higher mean birth weight (P=0.002), lower risk of low birth weight (<2500 g, P=0.02), older gestational age at delivery (P=0.009), and lower risk of premature birth (P=0.02).
However, there was no significant difference between the treatment groups with regard to birth-weight-for-gestational-age z score (P=0.20), neonatal length (P=0.07), head circumference (P=0.28), hemoglobin concentration in cord blood (P=0.14), cord blood ZPP-heme ratio (P=0.82), or cord erythrocyte ZPP-heme ratio (P=0.88).
Based on these results, the investigators said the benefits of universal iron supplementation during pregnancy (in countries where it is impractical to screen for iron status) outweigh the possible risks.
Photo by Nina Matthews
Taking iron supplements during pregnancy does not increase a woman’s risk of contracting malaria, according to research published in JAMA.
Investigators studied nearly 500 pregnant women in a malaria-endemic region, comparing those who received daily iron supplements to those who received placebo.
Roughly half of the women in each group developed malaria, and iron supplementation was associated with benefits for mothers and children.
Martin N. Mwangi, PhD, of Wageningen University in The Netherlands, and his colleagues conducted this research.
The team said current estimates suggest that anemia affects 57% of pregnant women in Africa. And although iron deficiency is the most common cause, iron supplementation during pregnancy has uncertain health benefits.
There is some evidence to suggest that iron supplementation may increase the risk of infectious diseases, including malaria.
To investigate this association, Dr Mwangi and his colleagues studied 470 pregnant women living in a malaria-endemic area in Kenya. The subjects were randomized to daily supplementation with 60 mg of iron (n=237) or placebo (n=233) until 1 month postpartum.
All women received 5.7 mg iron per day through flour fortification during the intervention, as well as the usual intermittent preventive treatment against malaria.
Among the 470 participating women, 40 women (22 in the iron group and 18 in the placebo group) were lost to follow-up or excluded at birth. Twelve mothers were lost to follow-up postpartum (5 iron, 7 placebo). At study entry, 190 of 318 women (60%) were iron-deficient.
After childbirth, there was no significant difference in Plasmodium infection between the treatment groups. Infection occurred in 50.9% of women in the iron group and 52.1% in the placebo group (P=0.83).
There was a significant increase in hemoglobin concentration and a significant decrease in anemia among mothers who received iron (P<0.001 for both). Mothers in the iron group also had a significantly lower mean zinc protoporphyrin (ZPP)-heme ratio in whole blood (P<0.001) and erythrocytes (P<0.001).
Children born to mothers in the iron group had a significantly higher mean birth weight (P=0.002), lower risk of low birth weight (<2500 g, P=0.02), older gestational age at delivery (P=0.009), and lower risk of premature birth (P=0.02).
However, there was no significant difference between the treatment groups with regard to birth-weight-for-gestational-age z score (P=0.20), neonatal length (P=0.07), head circumference (P=0.28), hemoglobin concentration in cord blood (P=0.14), cord blood ZPP-heme ratio (P=0.82), or cord erythrocyte ZPP-heme ratio (P=0.88).
Based on these results, the investigators said the benefits of universal iron supplementation during pregnancy (in countries where it is impractical to screen for iron status) outweigh the possible risks.
Photo by Nina Matthews
Taking iron supplements during pregnancy does not increase a woman’s risk of contracting malaria, according to research published in JAMA.
Investigators studied nearly 500 pregnant women in a malaria-endemic region, comparing those who received daily iron supplements to those who received placebo.
Roughly half of the women in each group developed malaria, and iron supplementation was associated with benefits for mothers and children.
Martin N. Mwangi, PhD, of Wageningen University in The Netherlands, and his colleagues conducted this research.
The team said current estimates suggest that anemia affects 57% of pregnant women in Africa. And although iron deficiency is the most common cause, iron supplementation during pregnancy has uncertain health benefits.
There is some evidence to suggest that iron supplementation may increase the risk of infectious diseases, including malaria.
To investigate this association, Dr Mwangi and his colleagues studied 470 pregnant women living in a malaria-endemic area in Kenya. The subjects were randomized to daily supplementation with 60 mg of iron (n=237) or placebo (n=233) until 1 month postpartum.
All women received 5.7 mg iron per day through flour fortification during the intervention, as well as the usual intermittent preventive treatment against malaria.
Among the 470 participating women, 40 women (22 in the iron group and 18 in the placebo group) were lost to follow-up or excluded at birth. Twelve mothers were lost to follow-up postpartum (5 iron, 7 placebo). At study entry, 190 of 318 women (60%) were iron-deficient.
After childbirth, there was no significant difference in Plasmodium infection between the treatment groups. Infection occurred in 50.9% of women in the iron group and 52.1% in the placebo group (P=0.83).
There was a significant increase in hemoglobin concentration and a significant decrease in anemia among mothers who received iron (P<0.001 for both). Mothers in the iron group also had a significantly lower mean zinc protoporphyrin (ZPP)-heme ratio in whole blood (P<0.001) and erythrocytes (P<0.001).
Children born to mothers in the iron group had a significantly higher mean birth weight (P=0.002), lower risk of low birth weight (<2500 g, P=0.02), older gestational age at delivery (P=0.009), and lower risk of premature birth (P=0.02).
However, there was no significant difference between the treatment groups with regard to birth-weight-for-gestational-age z score (P=0.20), neonatal length (P=0.07), head circumference (P=0.28), hemoglobin concentration in cord blood (P=0.14), cord blood ZPP-heme ratio (P=0.82), or cord erythrocyte ZPP-heme ratio (P=0.88).
Based on these results, the investigators said the benefits of universal iron supplementation during pregnancy (in countries where it is impractical to screen for iron status) outweigh the possible risks.
FDA approves drug to prevent delayed CINV in adults
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved rolapitant (Varubi) for use in adult cancer patients receiving initial and repeat courses of emetogenic chemotherapy.
Rolapitant is to be used in combination with other antiemetic agents to prevent delayed chemotherapy-induced nausea and vomiting (CINV).
Tesaro, Inc., the company developing rolapitant, plans to launch the drug in the fourth quarter of this year.
Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately 7 days. Activation of NK-1 receptors plays a central role in CINV, particularly in the delayed phase (the 25- to 120-hour period after chemotherapy administration).
Rolapitant comes in tablet form. The recommended dose is 180 mg, given approximately 1 to 2 hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone when administering rolapitant.
Rolapitant inhibits the CYP2D6 enzyme, so it is contraindicated with the use of thioridazine, a drug metabolized by the CYP2D6 enzyme. Use of these drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.
Rolapitant clinical trials
Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).
The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.
In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.
Highly emetogenic chemotherapy
The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were recently published in The Lancet Oncology.
Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.
In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).
In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).
The most common adverse events (≥3%) were neutropenia (9% rolapitant and 8% control), hiccups (5% and 4%), and abdominal pain (3% and 2%).
Moderately emetogenic chemotherapy
Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy regimens. Results from this trial were recently published in The Lancet Oncology.
This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).
The most common adverse events (≥3%) were decreased appetite (9% rolapitant and 7% control), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).
The full prescribing information for rolapitant is available at www.varubirx.com.
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved rolapitant (Varubi) for use in adult cancer patients receiving initial and repeat courses of emetogenic chemotherapy.
Rolapitant is to be used in combination with other antiemetic agents to prevent delayed chemotherapy-induced nausea and vomiting (CINV).
Tesaro, Inc., the company developing rolapitant, plans to launch the drug in the fourth quarter of this year.
Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately 7 days. Activation of NK-1 receptors plays a central role in CINV, particularly in the delayed phase (the 25- to 120-hour period after chemotherapy administration).
Rolapitant comes in tablet form. The recommended dose is 180 mg, given approximately 1 to 2 hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone when administering rolapitant.
Rolapitant inhibits the CYP2D6 enzyme, so it is contraindicated with the use of thioridazine, a drug metabolized by the CYP2D6 enzyme. Use of these drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.
Rolapitant clinical trials
Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).
The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.
In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.
Highly emetogenic chemotherapy
The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were recently published in The Lancet Oncology.
Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.
In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).
In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).
The most common adverse events (≥3%) were neutropenia (9% rolapitant and 8% control), hiccups (5% and 4%), and abdominal pain (3% and 2%).
Moderately emetogenic chemotherapy
Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy regimens. Results from this trial were recently published in The Lancet Oncology.
This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).
The most common adverse events (≥3%) were decreased appetite (9% rolapitant and 7% control), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).
The full prescribing information for rolapitant is available at www.varubirx.com.
Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved rolapitant (Varubi) for use in adult cancer patients receiving initial and repeat courses of emetogenic chemotherapy.
Rolapitant is to be used in combination with other antiemetic agents to prevent delayed chemotherapy-induced nausea and vomiting (CINV).
Tesaro, Inc., the company developing rolapitant, plans to launch the drug in the fourth quarter of this year.
Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately 7 days. Activation of NK-1 receptors plays a central role in CINV, particularly in the delayed phase (the 25- to 120-hour period after chemotherapy administration).
Rolapitant comes in tablet form. The recommended dose is 180 mg, given approximately 1 to 2 hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone when administering rolapitant.
Rolapitant inhibits the CYP2D6 enzyme, so it is contraindicated with the use of thioridazine, a drug metabolized by the CYP2D6 enzyme. Use of these drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.
Rolapitant clinical trials
Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).
The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.
In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.
Highly emetogenic chemotherapy
The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were recently published in The Lancet Oncology.
Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.
In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).
In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).
The most common adverse events (≥3%) were neutropenia (9% rolapitant and 8% control), hiccups (5% and 4%), and abdominal pain (3% and 2%).
Moderately emetogenic chemotherapy
Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy regimens. Results from this trial were recently published in The Lancet Oncology.
This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).
The most common adverse events (≥3%) were decreased appetite (9% rolapitant and 7% control), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).
The full prescribing information for rolapitant is available at www.varubirx.com.
How a toxin in wasp venom kills cancer cells
Polybia paulista
Photo by Mario Palma/
São Paulo State University
The wasp Polybia paulista protects itself from predators by producing venom known to contain a cancer-fighting toxin.
A study published in Biophysical Journal helps explain how the venom’s toxin, MP1 (Polybia-MP1), selectively kills cancer cells without harming normal cells.
MP1 interacts with lipids that are abnormally distributed on the surface of cancer cells, creating holes that facilitate the escape of molecules crucial for cell function.
“Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs,” said study author Paul Beales, PhD, of the University of Leeds in the UK.
MP1 is known to act against microbial pathogens by disrupting the bacterial cell membrane. The peptide has shown promise for treating cancers, as it can inhibit the growth of prostate and bladder cancer cells, as well as multi-drug resistant leukemic cells.
However, it has not been clear how MP1 selectively destroys cancer cells without harming normal cells. Dr Beales and his colleagues thought an explanation might lie in the unique properties of cancer cell membranes.
In healthy cell membranes, the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings.
The researchers tested their theory by creating model membranes, some of which contained PE and/or PS, and exposing them to MP1. They used a wide range of imaging and biophysical techniques to characterize MP1’s destructive effects on the membranes.
The team found that PS increased the binding of MP1 to the membrane by a factor of 7 to 8. On the other hand, PE enhanced MP1’s ability to quickly disrupt the membrane, increasing the size of holes by a factor of 20 to 30.
“Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells,” said study author João Ruggiero Neto, of São Paulo State University in Brazil.
“The dramatic enhancement of the permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising.”
In future studies, the researchers plan to alter MP1’s amino acid sequence to examine how the peptide’s structure relates to its function and further improve the peptide’s selectivity and potency for clinical purposes.
“Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine,” Dr Beales said.
“As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that.”
Polybia paulista
Photo by Mario Palma/
São Paulo State University
The wasp Polybia paulista protects itself from predators by producing venom known to contain a cancer-fighting toxin.
A study published in Biophysical Journal helps explain how the venom’s toxin, MP1 (Polybia-MP1), selectively kills cancer cells without harming normal cells.
MP1 interacts with lipids that are abnormally distributed on the surface of cancer cells, creating holes that facilitate the escape of molecules crucial for cell function.
“Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs,” said study author Paul Beales, PhD, of the University of Leeds in the UK.
MP1 is known to act against microbial pathogens by disrupting the bacterial cell membrane. The peptide has shown promise for treating cancers, as it can inhibit the growth of prostate and bladder cancer cells, as well as multi-drug resistant leukemic cells.
However, it has not been clear how MP1 selectively destroys cancer cells without harming normal cells. Dr Beales and his colleagues thought an explanation might lie in the unique properties of cancer cell membranes.
In healthy cell membranes, the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings.
The researchers tested their theory by creating model membranes, some of which contained PE and/or PS, and exposing them to MP1. They used a wide range of imaging and biophysical techniques to characterize MP1’s destructive effects on the membranes.
The team found that PS increased the binding of MP1 to the membrane by a factor of 7 to 8. On the other hand, PE enhanced MP1’s ability to quickly disrupt the membrane, increasing the size of holes by a factor of 20 to 30.
“Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells,” said study author João Ruggiero Neto, of São Paulo State University in Brazil.
“The dramatic enhancement of the permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising.”
In future studies, the researchers plan to alter MP1’s amino acid sequence to examine how the peptide’s structure relates to its function and further improve the peptide’s selectivity and potency for clinical purposes.
“Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine,” Dr Beales said.
“As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that.”
Polybia paulista
Photo by Mario Palma/
São Paulo State University
The wasp Polybia paulista protects itself from predators by producing venom known to contain a cancer-fighting toxin.
A study published in Biophysical Journal helps explain how the venom’s toxin, MP1 (Polybia-MP1), selectively kills cancer cells without harming normal cells.
MP1 interacts with lipids that are abnormally distributed on the surface of cancer cells, creating holes that facilitate the escape of molecules crucial for cell function.
“Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs,” said study author Paul Beales, PhD, of the University of Leeds in the UK.
MP1 is known to act against microbial pathogens by disrupting the bacterial cell membrane. The peptide has shown promise for treating cancers, as it can inhibit the growth of prostate and bladder cancer cells, as well as multi-drug resistant leukemic cells.
However, it has not been clear how MP1 selectively destroys cancer cells without harming normal cells. Dr Beales and his colleagues thought an explanation might lie in the unique properties of cancer cell membranes.
In healthy cell membranes, the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings.
The researchers tested their theory by creating model membranes, some of which contained PE and/or PS, and exposing them to MP1. They used a wide range of imaging and biophysical techniques to characterize MP1’s destructive effects on the membranes.
The team found that PS increased the binding of MP1 to the membrane by a factor of 7 to 8. On the other hand, PE enhanced MP1’s ability to quickly disrupt the membrane, increasing the size of holes by a factor of 20 to 30.
“Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells,” said study author João Ruggiero Neto, of São Paulo State University in Brazil.
“The dramatic enhancement of the permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising.”
In future studies, the researchers plan to alter MP1’s amino acid sequence to examine how the peptide’s structure relates to its function and further improve the peptide’s selectivity and potency for clinical purposes.
“Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine,” Dr Beales said.
“As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that.”
Public uninformed about cancer therapies, survey suggests
receiving chemotherapy
Photo by Rhoda Baer
Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.
Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.
But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.
Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.
The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.
The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.
Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.
Survey questions and responses were as follows.
Radiotherapy
Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?
| Intensity-modulated radiotherapy | 4% |
| Stereotactic radiotherapy/
stereotactic ablative radiotherapy |
3% |
| Image-guided radiotherapy | 9% |
| Proton beam therapy | 30% |
| Brachytherapy | 5% |
| Radiofrequency ablation | 7% |
| Cyberknife | 4% |
| Gammaknife | 6% |
| Higgs-boson radiotherapy
(red herring option) |
6% |
| Carbon ion radiotherapy
(red herring option) |
3% |
| None of these | 50% |
| Prefer not to say | 11% |
Other cancer treatments
Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?
| Immunotherapy | 19% |
| Personalized drugs | 29% |
| Monoclonal antibodies | 5% |
| High-dose chemotherapy
with stem cell transplant |
26% |
| Tablet chemotherapy | 28% |
| Molecular diagnostic tests | 6% |
| Robotically assisted surgery/Da Vinci robot | 12% |
| Laparoscopic (keyhole) surgery | 39% |
| None of these | 32% |
| Prefer not to say | 11% |
NHS funding
What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?
| Treatment | 1st priority | 2nd priority | 3rd priority | Lowest priority |
| Chemotherapy &
other drug treatments |
57% | 29% | 10% | 4% |
| Surgery | 29% | 35% | 31% | 5% |
| Radiotherapy | 9% | 32% | 53% | 5% |
| Alternative treatments | 5% | 4% | 6% | 86% |
receiving chemotherapy
Photo by Rhoda Baer
Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.
Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.
But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.
Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.
The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.
The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.
Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.
Survey questions and responses were as follows.
Radiotherapy
Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?
| Intensity-modulated radiotherapy | 4% |
| Stereotactic radiotherapy/
stereotactic ablative radiotherapy |
3% |
| Image-guided radiotherapy | 9% |
| Proton beam therapy | 30% |
| Brachytherapy | 5% |
| Radiofrequency ablation | 7% |
| Cyberknife | 4% |
| Gammaknife | 6% |
| Higgs-boson radiotherapy
(red herring option) |
6% |
| Carbon ion radiotherapy
(red herring option) |
3% |
| None of these | 50% |
| Prefer not to say | 11% |
Other cancer treatments
Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?
| Immunotherapy | 19% |
| Personalized drugs | 29% |
| Monoclonal antibodies | 5% |
| High-dose chemotherapy
with stem cell transplant |
26% |
| Tablet chemotherapy | 28% |
| Molecular diagnostic tests | 6% |
| Robotically assisted surgery/Da Vinci robot | 12% |
| Laparoscopic (keyhole) surgery | 39% |
| None of these | 32% |
| Prefer not to say | 11% |
NHS funding
What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?
| Treatment | 1st priority | 2nd priority | 3rd priority | Lowest priority |
| Chemotherapy &
other drug treatments |
57% | 29% | 10% | 4% |
| Surgery | 29% | 35% | 31% | 5% |
| Radiotherapy | 9% | 32% | 53% | 5% |
| Alternative treatments | 5% | 4% | 6% | 86% |
receiving chemotherapy
Photo by Rhoda Baer
Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.
Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.
But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.
Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.
The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.
The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.
Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.
Survey questions and responses were as follows.
Radiotherapy
Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?
| Intensity-modulated radiotherapy | 4% |
| Stereotactic radiotherapy/
stereotactic ablative radiotherapy |
3% |
| Image-guided radiotherapy | 9% |
| Proton beam therapy | 30% |
| Brachytherapy | 5% |
| Radiofrequency ablation | 7% |
| Cyberknife | 4% |
| Gammaknife | 6% |
| Higgs-boson radiotherapy
(red herring option) |
6% |
| Carbon ion radiotherapy
(red herring option) |
3% |
| None of these | 50% |
| Prefer not to say | 11% |
Other cancer treatments
Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?
| Immunotherapy | 19% |
| Personalized drugs | 29% |
| Monoclonal antibodies | 5% |
| High-dose chemotherapy
with stem cell transplant |
26% |
| Tablet chemotherapy | 28% |
| Molecular diagnostic tests | 6% |
| Robotically assisted surgery/Da Vinci robot | 12% |
| Laparoscopic (keyhole) surgery | 39% |
| None of these | 32% |
| Prefer not to say | 11% |
NHS funding
What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?
| Treatment | 1st priority | 2nd priority | 3rd priority | Lowest priority |
| Chemotherapy &
other drug treatments |
57% | 29% | 10% | 4% |
| Surgery | 29% | 35% | 31% | 5% |
| Radiotherapy | 9% | 32% | 53% | 5% |
| Alternative treatments | 5% | 4% | 6% | 86% |
Protein may be key in virus, cancer research
Image courtesy of the
University of North Carolina
Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.
The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.
The team believes this finding could have a range of therapeutic implications.
“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.
Dr Zhu and his colleagues described this research in Cell Host and Microbe.
The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”
To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”
Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.
The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.
Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.
When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.
For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.
Image courtesy of the
University of North Carolina
Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.
The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.
The team believes this finding could have a range of therapeutic implications.
“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.
Dr Zhu and his colleagues described this research in Cell Host and Microbe.
The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”
To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”
Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.
The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.
Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.
When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.
For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.
Image courtesy of the
University of North Carolina
Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.
The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.
The team believes this finding could have a range of therapeutic implications.
“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.
Dr Zhu and his colleagues described this research in Cell Host and Microbe.
The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”
To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”
Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.
The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.
Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.
When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.
For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.
Malaria tests underused despite training
Photo courtesy of USAID
A study conducted in Nigeria has shown that health providers continue to prescribe malaria medicines inappropriately, even after they learn to test for malaria and receive testing kits free of charge.
Health providers were given rapid diagnostic tests (RDT) for malaria and learned to use the tests via 3 different methods.
However, the use of RDTs was “critically low” in all 3 groups, as was the proportion of patients treated appropriately.
“This study confirms that treating malaria based on signs and symptoms alone remains an ingrained behavior that is difficult to change,” said Obinna Onwujekwe, MD, PhD, of the University of Nigeria in Enugu.
Dr Onwujekwe and his colleagues reported these findings in PLOS ONE.
Interventions
Their study included health workers and patients from 40 communities in the Nigerian state of Enugu. Health workers received free RDT kits and were taught to use the tests in 3 different ways.
The first group received comprehensive RDT training, which included instructions on how to use an RDT, guidelines on malaria diagnosis and treatment, information about other causes of fever, and help with communications skills, especially for patients whose test results were negative.
The second group received the same training plus a school-based intervention that involved training 2 teachers per school. The aim was to influence the attitudes of school children and their families as well as the wider community.
And health workers in the third group—the control arm—were invited to a demonstration and practical on how to safely use RDTs and supplied with written instructions on their use.
Results
The primary outcome was the proportion of patients who were treated according to guidelines. In other words, they presented with symptoms consistent with malaria, were tested for malaria, and received treatment consistent with the test result.
The researchers assessed the primary outcome in 4946 patients from 40 communities—12 in the control arm and 14 in each intervention arm.
There was no significant difference between the arms with regard to this outcome. The proportion of patients treated according to guidelines was 36% in the comprehensive training arm, 24% in the training-school arm, and 23% in the control arm (P=0.36).
Likewise, the use of testing was low in all arms—34% in the control arm, 48% in the training arm, and 37% in the training-school arm (P=0.47).
The use of testing was lower at private facilities than public ones. Cost may have been a factor here, as public facilities were asked to offer testing free of charge, but private facilities could charge 100 Naira (0.6 USD).
“We have shown that training alone is not enough to realize the full potential of an RDT,” said Virginia Wiseman, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“We must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines, especially in the private sector, where we found levels of testing to be lowest.”
Photo courtesy of USAID
A study conducted in Nigeria has shown that health providers continue to prescribe malaria medicines inappropriately, even after they learn to test for malaria and receive testing kits free of charge.
Health providers were given rapid diagnostic tests (RDT) for malaria and learned to use the tests via 3 different methods.
However, the use of RDTs was “critically low” in all 3 groups, as was the proportion of patients treated appropriately.
“This study confirms that treating malaria based on signs and symptoms alone remains an ingrained behavior that is difficult to change,” said Obinna Onwujekwe, MD, PhD, of the University of Nigeria in Enugu.
Dr Onwujekwe and his colleagues reported these findings in PLOS ONE.
Interventions
Their study included health workers and patients from 40 communities in the Nigerian state of Enugu. Health workers received free RDT kits and were taught to use the tests in 3 different ways.
The first group received comprehensive RDT training, which included instructions on how to use an RDT, guidelines on malaria diagnosis and treatment, information about other causes of fever, and help with communications skills, especially for patients whose test results were negative.
The second group received the same training plus a school-based intervention that involved training 2 teachers per school. The aim was to influence the attitudes of school children and their families as well as the wider community.
And health workers in the third group—the control arm—were invited to a demonstration and practical on how to safely use RDTs and supplied with written instructions on their use.
Results
The primary outcome was the proportion of patients who were treated according to guidelines. In other words, they presented with symptoms consistent with malaria, were tested for malaria, and received treatment consistent with the test result.
The researchers assessed the primary outcome in 4946 patients from 40 communities—12 in the control arm and 14 in each intervention arm.
There was no significant difference between the arms with regard to this outcome. The proportion of patients treated according to guidelines was 36% in the comprehensive training arm, 24% in the training-school arm, and 23% in the control arm (P=0.36).
Likewise, the use of testing was low in all arms—34% in the control arm, 48% in the training arm, and 37% in the training-school arm (P=0.47).
The use of testing was lower at private facilities than public ones. Cost may have been a factor here, as public facilities were asked to offer testing free of charge, but private facilities could charge 100 Naira (0.6 USD).
“We have shown that training alone is not enough to realize the full potential of an RDT,” said Virginia Wiseman, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“We must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines, especially in the private sector, where we found levels of testing to be lowest.”
Photo courtesy of USAID
A study conducted in Nigeria has shown that health providers continue to prescribe malaria medicines inappropriately, even after they learn to test for malaria and receive testing kits free of charge.
Health providers were given rapid diagnostic tests (RDT) for malaria and learned to use the tests via 3 different methods.
However, the use of RDTs was “critically low” in all 3 groups, as was the proportion of patients treated appropriately.
“This study confirms that treating malaria based on signs and symptoms alone remains an ingrained behavior that is difficult to change,” said Obinna Onwujekwe, MD, PhD, of the University of Nigeria in Enugu.
Dr Onwujekwe and his colleagues reported these findings in PLOS ONE.
Interventions
Their study included health workers and patients from 40 communities in the Nigerian state of Enugu. Health workers received free RDT kits and were taught to use the tests in 3 different ways.
The first group received comprehensive RDT training, which included instructions on how to use an RDT, guidelines on malaria diagnosis and treatment, information about other causes of fever, and help with communications skills, especially for patients whose test results were negative.
The second group received the same training plus a school-based intervention that involved training 2 teachers per school. The aim was to influence the attitudes of school children and their families as well as the wider community.
And health workers in the third group—the control arm—were invited to a demonstration and practical on how to safely use RDTs and supplied with written instructions on their use.
Results
The primary outcome was the proportion of patients who were treated according to guidelines. In other words, they presented with symptoms consistent with malaria, were tested for malaria, and received treatment consistent with the test result.
The researchers assessed the primary outcome in 4946 patients from 40 communities—12 in the control arm and 14 in each intervention arm.
There was no significant difference between the arms with regard to this outcome. The proportion of patients treated according to guidelines was 36% in the comprehensive training arm, 24% in the training-school arm, and 23% in the control arm (P=0.36).
Likewise, the use of testing was low in all arms—34% in the control arm, 48% in the training arm, and 37% in the training-school arm (P=0.47).
The use of testing was lower at private facilities than public ones. Cost may have been a factor here, as public facilities were asked to offer testing free of charge, but private facilities could charge 100 Naira (0.6 USD).
“We have shown that training alone is not enough to realize the full potential of an RDT,” said Virginia Wiseman, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“We must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines, especially in the private sector, where we found levels of testing to be lowest.”