Related Issues

Wallcur IV solution

Credit: FDA

The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) are still investigating multiple instances of Wallcur’s simulated intravenous (IV) saline products being administered to patients.

So far, more than 40 patients have received infusions of Wallcur’s simulated IV saline solution, Practi-0.9% sodium chloride solution, which is intended for training purposes only. The product is not sterile and should not be injected in humans or animals.

There have been many adverse events associated with the infusions, including fever, chills, tremors, and headache. Some patients were hospitalized, and there has been 1 death, although it’s not clear if this death is directly related to the product.

Adverse events have been reported in 7 states: Florida, Georgia, Idaho, Louisiana, North Carolina, New York, and Colorado.

The FDA, in partnership with the CDC, has collected samples of Wallcur Practi 0.9% sodium chloride solution from clinics and distributors. These products are being tested to determine if they caused the adverse events observed in patients.

In addition, Wallcur has initiated a voluntary recall of Practi-0.9% sodium chloride IV solutions.

Most medical facilities that received the product said they were unaware that the IV solution bags were simulation products. However, at least one clinic recognized the Wallcur product was a simulation product upon receipt and returned it to the distributor.

The FDA said it is working with distributors who sold the simulated IV products and clinics that purchased and administered the products from Wallcur to determine how these products entered the supply chain and were administered to patients.

While Sodium Chloride 0.9% Injection (normal saline) has been in short supply, the FDA has been working with manufacturers to end the shortage.

The FDA has allowed the temporary distribution of additional IV normal saline from alternate sources: Fresenius Kabi USA, Baxter Healthcare Corp., and B. Braun Medical Inc. Currently, normal saline is available from several manufacturers, as posted on the FDA’s website.

FDA recommendations

The FDA is encouraging healthcare providers to ensure IV solution simulation products are removed from office inventory to eliminate the possible injection of Wallcur simulated products into patients.

Providers should visually inspect all current IV saline solution bags to ensure none of the bags are labeled “Wallcur,” “Practi-products,” “For clinical simulation,” or “Not for use in human or animal patients.”

If you have products labeled with any of these words or suspect you may have received other products intended for training purposes, separate simulation products from existing inventory, and contact your distributor for directions on how to return these products.

If you have received Wallcur Practi-products by mistake, please contact the distributor, or Wallcur, LLC of San Diego for return instructions.

Consider reviewing your office procedures and make sure there are procedures in place to visually inspect all future shipments of normal saline products to ensure they are for clinical use.

If you suspect that any Wallcur training IV products may have been administered to a patient, whether or not the incident has resulted in an adverse event:

• Evaluate all potentially exposed patients with new or ongoing symptoms
• Use appropriate treatment
• Report suspected cases to the state health department
• Report any adverse events following the use of these products to the FDA’s MedWatch program online or at 1-800-332-1088.

Patients who believe they received an injection of Wallcur simulated IV solution should contact their healthcare provider.

Patients who received simulated IV saline experienced fever, chills, muscle aches, and headaches almost immediately upon injection, and some required hospitalization. In most reported cases, these signs and symptoms were immediately recognized, and patients received appropriate medical attention.

Wholesalers, distributors, and suppliers of IV saline products should inspect their inventory to ensure they are not distributing simulated products as clinical-use products.

If you suspect you may have distributed Wallcur simulated IV solution to clients by mistake, immediately attempt to recall the products and warn clients of the potential risks. You should also contact Wallcur and your distributor and file a report with the FDA’s MedWatch program.

Wallcur IV solution

Credit: FDA

The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) are still investigating multiple instances of Wallcur’s simulated intravenous (IV) saline products being administered to patients.

So far, more than 40 patients have received infusions of Wallcur’s simulated IV saline solution, Practi-0.9% sodium chloride solution, which is intended for training purposes only. The product is not sterile and should not be injected in humans or animals.

There have been many adverse events associated with the infusions, including fever, chills, tremors, and headache. Some patients were hospitalized, and there has been 1 death, although it’s not clear if this death is directly related to the product.

Adverse events have been reported in 7 states: Florida, Georgia, Idaho, Louisiana, North Carolina, New York, and Colorado.

The FDA, in partnership with the CDC, has collected samples of Wallcur Practi 0.9% sodium chloride solution from clinics and distributors. These products are being tested to determine if they caused the adverse events observed in patients.

In addition, Wallcur has initiated a voluntary recall of Practi-0.9% sodium chloride IV solutions.

Most medical facilities that received the product said they were unaware that the IV solution bags were simulation products. However, at least one clinic recognized the Wallcur product was a simulation product upon receipt and returned it to the distributor.

The FDA said it is working with distributors who sold the simulated IV products and clinics that purchased and administered the products from Wallcur to determine how these products entered the supply chain and were administered to patients.

While Sodium Chloride 0.9% Injection (normal saline) has been in short supply, the FDA has been working with manufacturers to end the shortage.

The FDA has allowed the temporary distribution of additional IV normal saline from alternate sources: Fresenius Kabi USA, Baxter Healthcare Corp., and B. Braun Medical Inc. Currently, normal saline is available from several manufacturers, as posted on the FDA’s website.

FDA recommendations

The FDA is encouraging healthcare providers to ensure IV solution simulation products are removed from office inventory to eliminate the possible injection of Wallcur simulated products into patients.

Providers should visually inspect all current IV saline solution bags to ensure none of the bags are labeled “Wallcur,” “Practi-products,” “For clinical simulation,” or “Not for use in human or animal patients.”

If you have products labeled with any of these words or suspect you may have received other products intended for training purposes, separate simulation products from existing inventory, and contact your distributor for directions on how to return these products.

If you have received Wallcur Practi-products by mistake, please contact the distributor, or Wallcur, LLC of San Diego for return instructions.

Consider reviewing your office procedures and make sure there are procedures in place to visually inspect all future shipments of normal saline products to ensure they are for clinical use.

If you suspect that any Wallcur training IV products may have been administered to a patient, whether or not the incident has resulted in an adverse event:

• Evaluate all potentially exposed patients with new or ongoing symptoms
• Use appropriate treatment
• Report suspected cases to the state health department
• Report any adverse events following the use of these products to the FDA’s MedWatch program online or at 1-800-332-1088.

Patients who believe they received an injection of Wallcur simulated IV solution should contact their healthcare provider.

Patients who received simulated IV saline experienced fever, chills, muscle aches, and headaches almost immediately upon injection, and some required hospitalization. In most reported cases, these signs and symptoms were immediately recognized, and patients received appropriate medical attention.

Wholesalers, distributors, and suppliers of IV saline products should inspect their inventory to ensure they are not distributing simulated products as clinical-use products.

If you suspect you may have distributed Wallcur simulated IV solution to clients by mistake, immediately attempt to recall the products and warn clients of the potential risks. You should also contact Wallcur and your distributor and file a report with the FDA’s MedWatch program.

Wallcur IV solution

Credit: FDA

The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) are still investigating multiple instances of Wallcur’s simulated intravenous (IV) saline products being administered to patients.

So far, more than 40 patients have received infusions of Wallcur’s simulated IV saline solution, Practi-0.9% sodium chloride solution, which is intended for training purposes only. The product is not sterile and should not be injected in humans or animals.

There have been many adverse events associated with the infusions, including fever, chills, tremors, and headache. Some patients were hospitalized, and there has been 1 death, although it’s not clear if this death is directly related to the product.

Adverse events have been reported in 7 states: Florida, Georgia, Idaho, Louisiana, North Carolina, New York, and Colorado.

The FDA, in partnership with the CDC, has collected samples of Wallcur Practi 0.9% sodium chloride solution from clinics and distributors. These products are being tested to determine if they caused the adverse events observed in patients.

In addition, Wallcur has initiated a voluntary recall of Practi-0.9% sodium chloride IV solutions.

Most medical facilities that received the product said they were unaware that the IV solution bags were simulation products. However, at least one clinic recognized the Wallcur product was a simulation product upon receipt and returned it to the distributor.

The FDA said it is working with distributors who sold the simulated IV products and clinics that purchased and administered the products from Wallcur to determine how these products entered the supply chain and were administered to patients.

While Sodium Chloride 0.9% Injection (normal saline) has been in short supply, the FDA has been working with manufacturers to end the shortage.

The FDA has allowed the temporary distribution of additional IV normal saline from alternate sources: Fresenius Kabi USA, Baxter Healthcare Corp., and B. Braun Medical Inc. Currently, normal saline is available from several manufacturers, as posted on the FDA’s website.

FDA recommendations

The FDA is encouraging healthcare providers to ensure IV solution simulation products are removed from office inventory to eliminate the possible injection of Wallcur simulated products into patients.

Providers should visually inspect all current IV saline solution bags to ensure none of the bags are labeled “Wallcur,” “Practi-products,” “For clinical simulation,” or “Not for use in human or animal patients.”

If you have products labeled with any of these words or suspect you may have received other products intended for training purposes, separate simulation products from existing inventory, and contact your distributor for directions on how to return these products.

If you have received Wallcur Practi-products by mistake, please contact the distributor, or Wallcur, LLC of San Diego for return instructions.

Consider reviewing your office procedures and make sure there are procedures in place to visually inspect all future shipments of normal saline products to ensure they are for clinical use.

If you suspect that any Wallcur training IV products may have been administered to a patient, whether or not the incident has resulted in an adverse event:

• Evaluate all potentially exposed patients with new or ongoing symptoms
• Use appropriate treatment
• Report suspected cases to the state health department
• Report any adverse events following the use of these products to the FDA’s MedWatch program online or at 1-800-332-1088.

Patients who believe they received an injection of Wallcur simulated IV solution should contact their healthcare provider.

Patients who received simulated IV saline experienced fever, chills, muscle aches, and headaches almost immediately upon injection, and some required hospitalization. In most reported cases, these signs and symptoms were immediately recognized, and patients received appropriate medical attention.

Wholesalers, distributors, and suppliers of IV saline products should inspect their inventory to ensure they are not distributing simulated products as clinical-use products.

If you suspect you may have distributed Wallcur simulated IV solution to clients by mistake, immediately attempt to recall the products and warn clients of the potential risks. You should also contact Wallcur and your distributor and file a report with the FDA’s MedWatch program.

Patient receives chemotherapy

through a central line

Credit: Rhoda Baer

Healthcare-associated infections (HAIs) are on the decline in the US, according to a report by the Centers for Disease Control and Prevention (CDC).

The data show that most types of HAIs have decreased in recent years, with a particularly large decrease in the rate of central line-associated bloodstream infections (CLABSIs).

The National and State Healthcare-associated Infection Progress Report is a snapshot of how each state and the country are doing in eliminating the infections that hospitals are required to report to the CDC.

The report summarizes data submitted to the CDC’s National Healthcare Safety Network, the nation’s HAI tracking system, which is used by more than 14,500 healthcare facilities across all 50 states, Washington, DC, and Puerto Rico.

“Hospitals have made real progress to reduce some types of healthcare-associated infections; it can be done,” said CDC Director Tom Frieden, MD.

“The key is for every hospital to have rigorous infection control programs to protect patients and healthcare workers, and for health care facilities and others to work together to reduce the many types of infections that haven’t decreased enough.”

On the national level, the report showed a 46% decrease in CLABSIs between 2008 and 2013. It also revealed a 19% decrease in surgical site infections related to the 10 procedures tracked in the report between 2008 and 2013.

There was an 8% decrease in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections between 2011 and 2013 and a 10% decrease in Clostridium difficile infections between 2011 and 2013.

However, there was a 6% increase in catheter-associated urinary tract infections since 2009.

Not all states reported or had enough data to calculate valid infection information on every infection in the report. But the CDC compared the number of infections reported to a national baseline.

And they found that 26 states performed better than the nation on at least 2 of the infection types. Sixteen states performed better than the nation on 3 or more infections, including 6 states performing better on 4 infections.

But 19 states performed worse than the nation on 2 infections, with 8 states performing worse on at least 3 infections.

The national baseline for HAIs will be reset at the end of 2015. Starting in 2016, HAI prevention progress from 2016 to 2020 will be measured in comparison to infection data from 2015.

Patient receives chemotherapy

through a central line

Credit: Rhoda Baer

Healthcare-associated infections (HAIs) are on the decline in the US, according to a report by the Centers for Disease Control and Prevention (CDC).

The data show that most types of HAIs have decreased in recent years, with a particularly large decrease in the rate of central line-associated bloodstream infections (CLABSIs).

The National and State Healthcare-associated Infection Progress Report is a snapshot of how each state and the country are doing in eliminating the infections that hospitals are required to report to the CDC.

The report summarizes data submitted to the CDC’s National Healthcare Safety Network, the nation’s HAI tracking system, which is used by more than 14,500 healthcare facilities across all 50 states, Washington, DC, and Puerto Rico.

“Hospitals have made real progress to reduce some types of healthcare-associated infections; it can be done,” said CDC Director Tom Frieden, MD.

“The key is for every hospital to have rigorous infection control programs to protect patients and healthcare workers, and for health care facilities and others to work together to reduce the many types of infections that haven’t decreased enough.”

On the national level, the report showed a 46% decrease in CLABSIs between 2008 and 2013. It also revealed a 19% decrease in surgical site infections related to the 10 procedures tracked in the report between 2008 and 2013.

There was an 8% decrease in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections between 2011 and 2013 and a 10% decrease in Clostridium difficile infections between 2011 and 2013.

However, there was a 6% increase in catheter-associated urinary tract infections since 2009.

Not all states reported or had enough data to calculate valid infection information on every infection in the report. But the CDC compared the number of infections reported to a national baseline.

And they found that 26 states performed better than the nation on at least 2 of the infection types. Sixteen states performed better than the nation on 3 or more infections, including 6 states performing better on 4 infections.

But 19 states performed worse than the nation on 2 infections, with 8 states performing worse on at least 3 infections.

The national baseline for HAIs will be reset at the end of 2015. Starting in 2016, HAI prevention progress from 2016 to 2020 will be measured in comparison to infection data from 2015.

Patient receives chemotherapy

through a central line

Credit: Rhoda Baer

Healthcare-associated infections (HAIs) are on the decline in the US, according to a report by the Centers for Disease Control and Prevention (CDC).

The data show that most types of HAIs have decreased in recent years, with a particularly large decrease in the rate of central line-associated bloodstream infections (CLABSIs).

The National and State Healthcare-associated Infection Progress Report is a snapshot of how each state and the country are doing in eliminating the infections that hospitals are required to report to the CDC.

The report summarizes data submitted to the CDC’s National Healthcare Safety Network, the nation’s HAI tracking system, which is used by more than 14,500 healthcare facilities across all 50 states, Washington, DC, and Puerto Rico.

“Hospitals have made real progress to reduce some types of healthcare-associated infections; it can be done,” said CDC Director Tom Frieden, MD.

“The key is for every hospital to have rigorous infection control programs to protect patients and healthcare workers, and for health care facilities and others to work together to reduce the many types of infections that haven’t decreased enough.”

On the national level, the report showed a 46% decrease in CLABSIs between 2008 and 2013. It also revealed a 19% decrease in surgical site infections related to the 10 procedures tracked in the report between 2008 and 2013.

There was an 8% decrease in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections between 2011 and 2013 and a 10% decrease in Clostridium difficile infections between 2011 and 2013.

However, there was a 6% increase in catheter-associated urinary tract infections since 2009.

Not all states reported or had enough data to calculate valid infection information on every infection in the report. But the CDC compared the number of infections reported to a national baseline.

And they found that 26 states performed better than the nation on at least 2 of the infection types. Sixteen states performed better than the nation on 3 or more infections, including 6 states performing better on 4 infections.

But 19 states performed worse than the nation on 2 infections, with 8 states performing worse on at least 3 infections.

The national baseline for HAIs will be reset at the end of 2015. Starting in 2016, HAI prevention progress from 2016 to 2020 will be measured in comparison to infection data from 2015.

Researchers in the lab

Credit: Rhoda Baer

An analysis of countries in North America, Europe, and Asia-Oceania showed that the US had the slowest annual growth in medical research funding from 2004 to 2011.

Nevertheless, the US was the leading sponsor of global medical research in 2011, accounting for 44% of the $265 billion spent in all the regions studied.

Hamilton Moses III, MD, of the Alerion Institute and Alerion Advisors LLC, in North Garden, Virginia, and his colleagues reported these discoveries in JAMA.

The researchers examined developments over the past 2 decades in the pattern of who conducts and who supports medical research, as well as resulting patents, publications, and new drug and device approvals.

The group compiled publicly available data from 1994 to 2012, showing trends in US and international research funding, productivity, and disease burden by source and industry type. Patents and publications (1981-2011) were evaluated using citation rates and impact factors.

International research funding

The researchers included data from the major countries of North America (US and Canada), Europe (including the 10 largest European countries in the

Organisation for Economic Co-operation and Development), and Asia-Oceania (Australia, China, India, Japan, Singapore, and South Korea).

Of these regions, the US had the lowest rate of annual growth in funding from 2004 to 2011 (1%). The rate was 4.1% in Europe, 4.5% in Canada, 6.8% in Japan, 9.3% in Australia, 16.9% in China, and 20.8% in the other Asian countries.

Still, in 2011, the US invested $117.2 billion (44%) of the $265 billion spent in all the regions studied. Europe spent $88.6 billion (33%), Japan spent $37.8 billion (14%), China spent $4.9 billion (1.2%), other Asian countries spent $9.7 billion (4%), Australia spent $3.8 billion (1.4%), and Canada spent $3.1 billion (1.2%).

Research outcomes

Dr Moses and his colleagues also compared other aspects of medical research among the regions, such as patent applications, research articles, and drug approvals.

They found that China filed 30% of global life science patent applications in 2011, while the US filed 24%. Japan filed the fewest applications of all the

regions analyzed.

The US and the European Union were neck-and-neck with regard to the share of biomedical research articles published in all regions in 2009—33.4% and 32.8%, respectively. China’s share was only 5%, but the country had the greatestgrowth in contribution from 2000 through 2009, at 18.7%.

And the European Medicines Agency (EMA) outstripped the US Food and Drug Administration (FDA) when it came to drug approvals. In 2013, the EMA approved 57 new molecular entities and biologics, compared to the FDA’s 27. From 2003 to2013, the FDA averaged 26 approvals per year, and the EMA averaged 42.

Researchers in the lab

Credit: Rhoda Baer

An analysis of countries in North America, Europe, and Asia-Oceania showed that the US had the slowest annual growth in medical research funding from 2004 to 2011.

Nevertheless, the US was the leading sponsor of global medical research in 2011, accounting for 44% of the $265 billion spent in all the regions studied.

Hamilton Moses III, MD, of the Alerion Institute and Alerion Advisors LLC, in North Garden, Virginia, and his colleagues reported these discoveries in JAMA.

The researchers examined developments over the past 2 decades in the pattern of who conducts and who supports medical research, as well as resulting patents, publications, and new drug and device approvals.

The group compiled publicly available data from 1994 to 2012, showing trends in US and international research funding, productivity, and disease burden by source and industry type. Patents and publications (1981-2011) were evaluated using citation rates and impact factors.

International research funding

The researchers included data from the major countries of North America (US and Canada), Europe (including the 10 largest European countries in the

Organisation for Economic Co-operation and Development), and Asia-Oceania (Australia, China, India, Japan, Singapore, and South Korea).

Of these regions, the US had the lowest rate of annual growth in funding from 2004 to 2011 (1%). The rate was 4.1% in Europe, 4.5% in Canada, 6.8% in Japan, 9.3% in Australia, 16.9% in China, and 20.8% in the other Asian countries.

Still, in 2011, the US invested $117.2 billion (44%) of the $265 billion spent in all the regions studied. Europe spent $88.6 billion (33%), Japan spent $37.8 billion (14%), China spent $4.9 billion (1.2%), other Asian countries spent $9.7 billion (4%), Australia spent $3.8 billion (1.4%), and Canada spent $3.1 billion (1.2%).

Research outcomes

Dr Moses and his colleagues also compared other aspects of medical research among the regions, such as patent applications, research articles, and drug approvals.

They found that China filed 30% of global life science patent applications in 2011, while the US filed 24%. Japan filed the fewest applications of all the

regions analyzed.

The US and the European Union were neck-and-neck with regard to the share of biomedical research articles published in all regions in 2009—33.4% and 32.8%, respectively. China’s share was only 5%, but the country had the greatestgrowth in contribution from 2000 through 2009, at 18.7%.

And the European Medicines Agency (EMA) outstripped the US Food and Drug Administration (FDA) when it came to drug approvals. In 2013, the EMA approved 57 new molecular entities and biologics, compared to the FDA’s 27. From 2003 to2013, the FDA averaged 26 approvals per year, and the EMA averaged 42.

Researchers in the lab

Credit: Rhoda Baer

An analysis of countries in North America, Europe, and Asia-Oceania showed that the US had the slowest annual growth in medical research funding from 2004 to 2011.

Nevertheless, the US was the leading sponsor of global medical research in 2011, accounting for 44% of the $265 billion spent in all the regions studied.

Hamilton Moses III, MD, of the Alerion Institute and Alerion Advisors LLC, in North Garden, Virginia, and his colleagues reported these discoveries in JAMA.

The researchers examined developments over the past 2 decades in the pattern of who conducts and who supports medical research, as well as resulting patents, publications, and new drug and device approvals.

The group compiled publicly available data from 1994 to 2012, showing trends in US and international research funding, productivity, and disease burden by source and industry type. Patents and publications (1981-2011) were evaluated using citation rates and impact factors.

International research funding

The researchers included data from the major countries of North America (US and Canada), Europe (including the 10 largest European countries in the

Organisation for Economic Co-operation and Development), and Asia-Oceania (Australia, China, India, Japan, Singapore, and South Korea).

Of these regions, the US had the lowest rate of annual growth in funding from 2004 to 2011 (1%). The rate was 4.1% in Europe, 4.5% in Canada, 6.8% in Japan, 9.3% in Australia, 16.9% in China, and 20.8% in the other Asian countries.

Still, in 2011, the US invested $117.2 billion (44%) of the $265 billion spent in all the regions studied. Europe spent $88.6 billion (33%), Japan spent $37.8 billion (14%), China spent $4.9 billion (1.2%), other Asian countries spent $9.7 billion (4%), Australia spent $3.8 billion (1.4%), and Canada spent $3.1 billion (1.2%).

Research outcomes

Dr Moses and his colleagues also compared other aspects of medical research among the regions, such as patent applications, research articles, and drug approvals.

They found that China filed 30% of global life science patent applications in 2011, while the US filed 24%. Japan filed the fewest applications of all the

regions analyzed.

The US and the European Union were neck-and-neck with regard to the share of biomedical research articles published in all regions in 2009—33.4% and 32.8%, respectively. China’s share was only 5%, but the country had the greatestgrowth in contribution from 2000 through 2009, at 18.7%.

And the European Medicines Agency (EMA) outstripped the US Food and Drug Administration (FDA) when it came to drug approvals. In 2013, the EMA approved 57 new molecular entities and biologics, compared to the FDA’s 27. From 2003 to2013, the FDA averaged 26 approvals per year, and the EMA averaged 42.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Lab mouse

Regulatory T cells (Tregs) need T-cell receptors to fulfill their protective functions, according to research published in Immunity.

The researchers knew that Tregs need T-cell receptors to develop properly, but they were unsure of the receptors’ role after that.

To find out, the team deactivated T-cell receptors on mature Tregs in genetically modified mice.

They found these defective Tregs were not able to carry out their protective function without the T-cell receptors.

Furthermore, the Treg pool fell significantly, as these cells were no longer multiplying.

However, the researchers also discovered that two of Tregs’ most well-known central molecular properties—the production of Foxp3 protein and specific chemical changes to DNA—were still present in the defective T cells.

“Without their receptor, the Tregs are still clearly identifiable as Tregs,” said study author Christoph Vahl, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany.

“However, they lose a large part of their cellular identity. They also lose their special ability to suppress excessive immune reactions.”

“The Tregs obviously need continuous contact with their environment to function correctly. This is presumably the reason why they need a receptor that recognizes endogenous substances and continuously sends signals.”

“During the course of our research, we uncovered a very important mechanism for suppressing excessive responses and responses targeted against the human body,” added Marc Schmidt-Supprian, PhD, also of the Max Planck Institute.

“These findings could be relevant for situations where it would be beneficial to weaken the control of Tregs over immune responses—for example, in the treatment of cancer.”

Lab mouse

Regulatory T cells (Tregs) need T-cell receptors to fulfill their protective functions, according to research published in Immunity.

The researchers knew that Tregs need T-cell receptors to develop properly, but they were unsure of the receptors’ role after that.

To find out, the team deactivated T-cell receptors on mature Tregs in genetically modified mice.

They found these defective Tregs were not able to carry out their protective function without the T-cell receptors.

Furthermore, the Treg pool fell significantly, as these cells were no longer multiplying.

However, the researchers also discovered that two of Tregs’ most well-known central molecular properties—the production of Foxp3 protein and specific chemical changes to DNA—were still present in the defective T cells.

“Without their receptor, the Tregs are still clearly identifiable as Tregs,” said study author Christoph Vahl, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany.

“However, they lose a large part of their cellular identity. They also lose their special ability to suppress excessive immune reactions.”

“The Tregs obviously need continuous contact with their environment to function correctly. This is presumably the reason why they need a receptor that recognizes endogenous substances and continuously sends signals.”

“During the course of our research, we uncovered a very important mechanism for suppressing excessive responses and responses targeted against the human body,” added Marc Schmidt-Supprian, PhD, also of the Max Planck Institute.

“These findings could be relevant for situations where it would be beneficial to weaken the control of Tregs over immune responses—for example, in the treatment of cancer.”

Lab mouse

Regulatory T cells (Tregs) need T-cell receptors to fulfill their protective functions, according to research published in Immunity.

The researchers knew that Tregs need T-cell receptors to develop properly, but they were unsure of the receptors’ role after that.

To find out, the team deactivated T-cell receptors on mature Tregs in genetically modified mice.

They found these defective Tregs were not able to carry out their protective function without the T-cell receptors.

Furthermore, the Treg pool fell significantly, as these cells were no longer multiplying.

However, the researchers also discovered that two of Tregs’ most well-known central molecular properties—the production of Foxp3 protein and specific chemical changes to DNA—were still present in the defective T cells.

“Without their receptor, the Tregs are still clearly identifiable as Tregs,” said study author Christoph Vahl, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany.

“However, they lose a large part of their cellular identity. They also lose their special ability to suppress excessive immune reactions.”

“The Tregs obviously need continuous contact with their environment to function correctly. This is presumably the reason why they need a receptor that recognizes endogenous substances and continuously sends signals.”

“During the course of our research, we uncovered a very important mechanism for suppressing excessive responses and responses targeted against the human body,” added Marc Schmidt-Supprian, PhD, also of the Max Planck Institute.

“These findings could be relevant for situations where it would be beneficial to weaken the control of Tregs over immune responses—for example, in the treatment of cancer.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research shows that, even decades after being cured, many cancer survivors face challenges resulting from their disease and its treatment.

A survey of more than 1500 cancer survivors revealed 16 themes of challenges or unmet needs, such as physical dysfunction, financial problems, a lack of education about cancer survival, and anxiety about cancer recurrence.

Mary Ann Burg, PhD, of the University of Central Florida in Orlando, and her colleagues reported these findings in Cancer.

To assess the unmet needs of cancer survivors, the researchers evaluated responses from an American Cancer Society survey in which subjects responded to the open-ended question, “Please tell us about any needs you have now as a cancer survivor that are not being met to your satisfaction.”

There were a total of 1514 respondents who were 2, 5, or 10 years from cancer diagnosis. They were 24 to 97 years of age, 65.4% were female, and 24.8% were racial/ethnic minorities (black and Hispanic/Latino).

“This study was unique in that it gave a very large sample of cancer survivors a real voice to express their needs and concerns,” Dr Burg said.

The researchers found that the number and type of challenges/unmet needs were not associated with a subject’s time since cancer treatment, although older cancer survivors tended to report fewer unmet needs than younger survivors.

Sixteen themes of challenges/unmet needs emerged from respondents’ answers, with physical issues being the most common. About 38% of respondents reported physical issues, such as pain, symptoms, and sexual dysfunction.

About 20% reported financial problems, such as issues with insurance and the affordability of needed services and products. About 20% also said they had needs related to unanswered questions and a lack of knowledge about what to expect as a cancer survivor, including guidance on follow-up care and cancer risks, causes, and prevention.

About 16% of respondents cited issues relating to personal control (a lack of physical and social autonomy). And about 16% described flaws and constraints in the healthcare system that affected early detection, diagnosis, treatment, follow-up care, and continuity of care.

About 14% of respondents reported a lack of resources (such as supplies, equipment, and medications), and about 14% cited emotional and mental health issues (such as fear of cancer recurrence, depression, and anxiety).

About 13% of respondents said they lacked social support (such as access to support groups), and 10% reported issues relating to societal perceptions of cancer survivors (such as discrimination and misinformation).

About 9% of respondents expressed the need to talk about or explain the cancer experience with their physician, friends, and family. And about 9% cited a lack of trust in healthcare providers.

Other themes included the wish for more effective cancer treatments (3.5%), body image issues such as feeling unattractive or losing trust in the body (3.5%), issues with the “survivor” identity (3.1%), trouble obtaining or maintaining appropriate employment (2.3%), and existential issues, such as finding meaning in the cancer experience (0.6%).

“Overall, we found that cancer survivors are often caught off guard by the lingering problems they experience after cancer treatment,” Dr Burg said. “In the wake of cancer, many survivors feel they have lost a sense of personal control, have reduced quality of life, and are frustrated that these problems are not sufficiently addressed within the medical care system.”

She added that this study points to several areas in which we might work to improve the situation, including raising public awareness of cancer survivors’ problems, promoting honest professional communication about the side effects of cancer and its treatment, and coordinating medical care resources to help survivors and their families cope with lingering challenges.

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research shows that, even decades after being cured, many cancer survivors face challenges resulting from their disease and its treatment.

A survey of more than 1500 cancer survivors revealed 16 themes of challenges or unmet needs, such as physical dysfunction, financial problems, a lack of education about cancer survival, and anxiety about cancer recurrence.

Mary Ann Burg, PhD, of the University of Central Florida in Orlando, and her colleagues reported these findings in Cancer.

To assess the unmet needs of cancer survivors, the researchers evaluated responses from an American Cancer Society survey in which subjects responded to the open-ended question, “Please tell us about any needs you have now as a cancer survivor that are not being met to your satisfaction.”

There were a total of 1514 respondents who were 2, 5, or 10 years from cancer diagnosis. They were 24 to 97 years of age, 65.4% were female, and 24.8% were racial/ethnic minorities (black and Hispanic/Latino).

“This study was unique in that it gave a very large sample of cancer survivors a real voice to express their needs and concerns,” Dr Burg said.

The researchers found that the number and type of challenges/unmet needs were not associated with a subject’s time since cancer treatment, although older cancer survivors tended to report fewer unmet needs than younger survivors.

Sixteen themes of challenges/unmet needs emerged from respondents’ answers, with physical issues being the most common. About 38% of respondents reported physical issues, such as pain, symptoms, and sexual dysfunction.

About 20% reported financial problems, such as issues with insurance and the affordability of needed services and products. About 20% also said they had needs related to unanswered questions and a lack of knowledge about what to expect as a cancer survivor, including guidance on follow-up care and cancer risks, causes, and prevention.

About 16% of respondents cited issues relating to personal control (a lack of physical and social autonomy). And about 16% described flaws and constraints in the healthcare system that affected early detection, diagnosis, treatment, follow-up care, and continuity of care.

About 14% of respondents reported a lack of resources (such as supplies, equipment, and medications), and about 14% cited emotional and mental health issues (such as fear of cancer recurrence, depression, and anxiety).

About 13% of respondents said they lacked social support (such as access to support groups), and 10% reported issues relating to societal perceptions of cancer survivors (such as discrimination and misinformation).

About 9% of respondents expressed the need to talk about or explain the cancer experience with their physician, friends, and family. And about 9% cited a lack of trust in healthcare providers.

Other themes included the wish for more effective cancer treatments (3.5%), body image issues such as feeling unattractive or losing trust in the body (3.5%), issues with the “survivor” identity (3.1%), trouble obtaining or maintaining appropriate employment (2.3%), and existential issues, such as finding meaning in the cancer experience (0.6%).

“Overall, we found that cancer survivors are often caught off guard by the lingering problems they experience after cancer treatment,” Dr Burg said. “In the wake of cancer, many survivors feel they have lost a sense of personal control, have reduced quality of life, and are frustrated that these problems are not sufficiently addressed within the medical care system.”

She added that this study points to several areas in which we might work to improve the situation, including raising public awareness of cancer survivors’ problems, promoting honest professional communication about the side effects of cancer and its treatment, and coordinating medical care resources to help survivors and their families cope with lingering challenges.

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research shows that, even decades after being cured, many cancer survivors face challenges resulting from their disease and its treatment.

A survey of more than 1500 cancer survivors revealed 16 themes of challenges or unmet needs, such as physical dysfunction, financial problems, a lack of education about cancer survival, and anxiety about cancer recurrence.

Mary Ann Burg, PhD, of the University of Central Florida in Orlando, and her colleagues reported these findings in Cancer.

To assess the unmet needs of cancer survivors, the researchers evaluated responses from an American Cancer Society survey in which subjects responded to the open-ended question, “Please tell us about any needs you have now as a cancer survivor that are not being met to your satisfaction.”

There were a total of 1514 respondents who were 2, 5, or 10 years from cancer diagnosis. They were 24 to 97 years of age, 65.4% were female, and 24.8% were racial/ethnic minorities (black and Hispanic/Latino).

“This study was unique in that it gave a very large sample of cancer survivors a real voice to express their needs and concerns,” Dr Burg said.

The researchers found that the number and type of challenges/unmet needs were not associated with a subject’s time since cancer treatment, although older cancer survivors tended to report fewer unmet needs than younger survivors.

Sixteen themes of challenges/unmet needs emerged from respondents’ answers, with physical issues being the most common. About 38% of respondents reported physical issues, such as pain, symptoms, and sexual dysfunction.

About 20% reported financial problems, such as issues with insurance and the affordability of needed services and products. About 20% also said they had needs related to unanswered questions and a lack of knowledge about what to expect as a cancer survivor, including guidance on follow-up care and cancer risks, causes, and prevention.

About 16% of respondents cited issues relating to personal control (a lack of physical and social autonomy). And about 16% described flaws and constraints in the healthcare system that affected early detection, diagnosis, treatment, follow-up care, and continuity of care.

About 14% of respondents reported a lack of resources (such as supplies, equipment, and medications), and about 14% cited emotional and mental health issues (such as fear of cancer recurrence, depression, and anxiety).

About 13% of respondents said they lacked social support (such as access to support groups), and 10% reported issues relating to societal perceptions of cancer survivors (such as discrimination and misinformation).

About 9% of respondents expressed the need to talk about or explain the cancer experience with their physician, friends, and family. And about 9% cited a lack of trust in healthcare providers.

Other themes included the wish for more effective cancer treatments (3.5%), body image issues such as feeling unattractive or losing trust in the body (3.5%), issues with the “survivor” identity (3.1%), trouble obtaining or maintaining appropriate employment (2.3%), and existential issues, such as finding meaning in the cancer experience (0.6%).

“Overall, we found that cancer survivors are often caught off guard by the lingering problems they experience after cancer treatment,” Dr Burg said. “In the wake of cancer, many survivors feel they have lost a sense of personal control, have reduced quality of life, and are frustrated that these problems are not sufficiently addressed within the medical care system.”

She added that this study points to several areas in which we might work to improve the situation, including raising public awareness of cancer survivors’ problems, promoting honest professional communication about the side effects of cancer and its treatment, and coordinating medical care resources to help survivors and their families cope with lingering challenges.

Syringe

A study of more than 2000 patients refutes the idea that biopsies cause cancer to spread.

In a study published in Gut, researchers showed that patients who received a biopsy had better overall survival and similar cancer-free survival rates as patients who did not have a biopsy.

The team studied pancreatic cancer but said their findings likely apply to other cancers because the diagnostic technique used in this study—fine needle aspiration—is commonly used across tumor types.

“This study shows that physicians and patients should feel reassured that a biopsy is very safe,” said study author Michael Wallace, MD, of the Mayo Clinic in Jacksonville, Florida.

“We do millions of biopsies of cancer a year in the US, but one or two case studies have led to this common myth that biopsies spread cancer.”

This is the second study Dr Wallace and his team have conducted to examine the risk of biopsy.

In a 2013 study published in Endoscopy, the researchers examined outcomes in 256 pancreatic cancer patients treated at the Mayo Clinic in Jacksonville. The team found no difference in cancer recurrence between 208 patients who had ultrasound-guided fine needle aspiration (EUS-FNA) and the 48 patients who did not have a biopsy.

In the current study, the researchers examined 11 years (1998-2009) of Medicare data on patients with non-metastatic pancreatic cancer who underwent surgery. The team examined overall survival and pancreatic cancer-specific survival in 498 patients who had EUS-FNA and in 1536 patients who did not have a biopsy.

During a mean follow-up time of 21 months, 285 patients (57%) in the EUS-FNA group and 1167 patients (76%) in the non-EUS-FNA group died. Pancreatic cancer was identified as the cause of death for 251 patients (50%) in the EUS-FNA group and 980 patients (64%) in the non-EUS-FNA group.

The median overall survival in the EUS-FNA group was 22 months, compared to 15 months in the non-EUS-FNA group. Multivariate analysis showed that receipt of EUS-FNA had a borderline significant association with improved overall survival (hazard ratio=0.84, P=0.03).

The median cancer-specific survival was 24 months in the EUS-FNA group and 18 months in the non-EUS-FNA group. Multivariate analysis revealed no significant difference between the two groups (hazard ratio=0.87, P=0.12).

“[Biopsies provide] very valuable information that allow us to tailor treatment,” Dr Wallace noted. “In some cases, we can offer chemotherapy and radiation before surgery for a better outcome, and, in other cases, we can avoid surgery and other therapy altogether.”

Syringe

A study of more than 2000 patients refutes the idea that biopsies cause cancer to spread.

In a study published in Gut, researchers showed that patients who received a biopsy had better overall survival and similar cancer-free survival rates as patients who did not have a biopsy.

The team studied pancreatic cancer but said their findings likely apply to other cancers because the diagnostic technique used in this study—fine needle aspiration—is commonly used across tumor types.

“This study shows that physicians and patients should feel reassured that a biopsy is very safe,” said study author Michael Wallace, MD, of the Mayo Clinic in Jacksonville, Florida.

“We do millions of biopsies of cancer a year in the US, but one or two case studies have led to this common myth that biopsies spread cancer.”

This is the second study Dr Wallace and his team have conducted to examine the risk of biopsy.

In a 2013 study published in Endoscopy, the researchers examined outcomes in 256 pancreatic cancer patients treated at the Mayo Clinic in Jacksonville. The team found no difference in cancer recurrence between 208 patients who had ultrasound-guided fine needle aspiration (EUS-FNA) and the 48 patients who did not have a biopsy.

In the current study, the researchers examined 11 years (1998-2009) of Medicare data on patients with non-metastatic pancreatic cancer who underwent surgery. The team examined overall survival and pancreatic cancer-specific survival in 498 patients who had EUS-FNA and in 1536 patients who did not have a biopsy.

During a mean follow-up time of 21 months, 285 patients (57%) in the EUS-FNA group and 1167 patients (76%) in the non-EUS-FNA group died. Pancreatic cancer was identified as the cause of death for 251 patients (50%) in the EUS-FNA group and 980 patients (64%) in the non-EUS-FNA group.

The median overall survival in the EUS-FNA group was 22 months, compared to 15 months in the non-EUS-FNA group. Multivariate analysis showed that receipt of EUS-FNA had a borderline significant association with improved overall survival (hazard ratio=0.84, P=0.03).

The median cancer-specific survival was 24 months in the EUS-FNA group and 18 months in the non-EUS-FNA group. Multivariate analysis revealed no significant difference between the two groups (hazard ratio=0.87, P=0.12).

“[Biopsies provide] very valuable information that allow us to tailor treatment,” Dr Wallace noted. “In some cases, we can offer chemotherapy and radiation before surgery for a better outcome, and, in other cases, we can avoid surgery and other therapy altogether.”

Syringe

A study of more than 2000 patients refutes the idea that biopsies cause cancer to spread.

In a study published in Gut, researchers showed that patients who received a biopsy had better overall survival and similar cancer-free survival rates as patients who did not have a biopsy.

The team studied pancreatic cancer but said their findings likely apply to other cancers because the diagnostic technique used in this study—fine needle aspiration—is commonly used across tumor types.

“This study shows that physicians and patients should feel reassured that a biopsy is very safe,” said study author Michael Wallace, MD, of the Mayo Clinic in Jacksonville, Florida.

“We do millions of biopsies of cancer a year in the US, but one or two case studies have led to this common myth that biopsies spread cancer.”

This is the second study Dr Wallace and his team have conducted to examine the risk of biopsy.

In a 2013 study published in Endoscopy, the researchers examined outcomes in 256 pancreatic cancer patients treated at the Mayo Clinic in Jacksonville. The team found no difference in cancer recurrence between 208 patients who had ultrasound-guided fine needle aspiration (EUS-FNA) and the 48 patients who did not have a biopsy.

In the current study, the researchers examined 11 years (1998-2009) of Medicare data on patients with non-metastatic pancreatic cancer who underwent surgery. The team examined overall survival and pancreatic cancer-specific survival in 498 patients who had EUS-FNA and in 1536 patients who did not have a biopsy.

During a mean follow-up time of 21 months, 285 patients (57%) in the EUS-FNA group and 1167 patients (76%) in the non-EUS-FNA group died. Pancreatic cancer was identified as the cause of death for 251 patients (50%) in the EUS-FNA group and 980 patients (64%) in the non-EUS-FNA group.

The median overall survival in the EUS-FNA group was 22 months, compared to 15 months in the non-EUS-FNA group. Multivariate analysis showed that receipt of EUS-FNA had a borderline significant association with improved overall survival (hazard ratio=0.84, P=0.03).

The median cancer-specific survival was 24 months in the EUS-FNA group and 18 months in the non-EUS-FNA group. Multivariate analysis revealed no significant difference between the two groups (hazard ratio=0.87, P=0.12).

“[Biopsies provide] very valuable information that allow us to tailor treatment,” Dr Wallace noted. “In some cases, we can offer chemotherapy and radiation before surgery for a better outcome, and, in other cases, we can avoid surgery and other therapy altogether.”

Lab mouse

Sepsis may have an Achilles heel that would allow for more effective treatment of the condition, according to research published in The FASEB Journal.

The study showed that CD39, an enzyme capable of clearing high levels of adenosine triphosphate (ATP) from the bloodstream, significantly improved survival of mice with severe sepsis.

Based on this finding, the researchers speculate that CD39 may also be used in other diseases associated with inflammation.

“Although we have come a long way in the treatment of sepsis since it was first described by Hippocrates in the fourth century BC, about 250,000 Americans still die from sepsis each year,” said study author Gyorgy Hasko, PhD, of Rutgers New Jersey Medical School in Newark.

“A drug that could cure patients with sepsis would not only save the lives of many, it would also decrease the enormous costs associated with treating septic patients in the intensive care unit and would help unburden the healthcare system.”

To make their discovery, Dr Hasko and his colleagues compared mice lacking the CD39 gene to wild-type mice. When sepsis was induced in both sets of mice, those without CD39 had worse survival.

With this information in hand, the researchers then performed another experiment with two more groups of normal mice that were septic.

The first group was injected with CD39 and the other with placebo. The mice that received CD39 had improved survival compared to those injected with placebo.

“Finding a more effective treatment for sepsis would be a major step forward since far too many people still die from overwhelming microbial infection,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. “If CD39 proves to be as critical a factor in humans as in mice, this is a major discovery.”

Lab mouse

Sepsis may have an Achilles heel that would allow for more effective treatment of the condition, according to research published in The FASEB Journal.

The study showed that CD39, an enzyme capable of clearing high levels of adenosine triphosphate (ATP) from the bloodstream, significantly improved survival of mice with severe sepsis.

Based on this finding, the researchers speculate that CD39 may also be used in other diseases associated with inflammation.

“Although we have come a long way in the treatment of sepsis since it was first described by Hippocrates in the fourth century BC, about 250,000 Americans still die from sepsis each year,” said study author Gyorgy Hasko, PhD, of Rutgers New Jersey Medical School in Newark.

“A drug that could cure patients with sepsis would not only save the lives of many, it would also decrease the enormous costs associated with treating septic patients in the intensive care unit and would help unburden the healthcare system.”

To make their discovery, Dr Hasko and his colleagues compared mice lacking the CD39 gene to wild-type mice. When sepsis was induced in both sets of mice, those without CD39 had worse survival.

With this information in hand, the researchers then performed another experiment with two more groups of normal mice that were septic.

The first group was injected with CD39 and the other with placebo. The mice that received CD39 had improved survival compared to those injected with placebo.

“Finding a more effective treatment for sepsis would be a major step forward since far too many people still die from overwhelming microbial infection,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. “If CD39 proves to be as critical a factor in humans as in mice, this is a major discovery.”

Lab mouse

Sepsis may have an Achilles heel that would allow for more effective treatment of the condition, according to research published in The FASEB Journal.

The study showed that CD39, an enzyme capable of clearing high levels of adenosine triphosphate (ATP) from the bloodstream, significantly improved survival of mice with severe sepsis.

Based on this finding, the researchers speculate that CD39 may also be used in other diseases associated with inflammation.

“Although we have come a long way in the treatment of sepsis since it was first described by Hippocrates in the fourth century BC, about 250,000 Americans still die from sepsis each year,” said study author Gyorgy Hasko, PhD, of Rutgers New Jersey Medical School in Newark.

“A drug that could cure patients with sepsis would not only save the lives of many, it would also decrease the enormous costs associated with treating septic patients in the intensive care unit and would help unburden the healthcare system.”

To make their discovery, Dr Hasko and his colleagues compared mice lacking the CD39 gene to wild-type mice. When sepsis was induced in both sets of mice, those without CD39 had worse survival.

With this information in hand, the researchers then performed another experiment with two more groups of normal mice that were septic.

The first group was injected with CD39 and the other with placebo. The mice that received CD39 had improved survival compared to those injected with placebo.

“Finding a more effective treatment for sepsis would be a major step forward since far too many people still die from overwhelming microbial infection,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. “If CD39 proves to be as critical a factor in humans as in mice, this is a major discovery.”

Colony of iPSCs

Credit: Salk Institute

The gene-editing technology CRISPR can precisely and efficiently alter human stem cells, according to research published in Molecular Therapy.

Using JAK2 and other genes as models, researchers showed that CRISPR offers advantages over TALEN, another gene-editing technique, for manipulating induced pluripotent stem cells (iPSCs).

And, unlike in a previous study, CRISPR did not produce any off-target effects.

The team believes their findings could streamline and speed up efforts to modify human iPSCs for use as treatments or in the development of model systems to study diseases and test drugs.

“Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs for human therapy aren’t that far away,” said study author Zhaohui Ye, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells.”

CRISPR originated from a microbial immune system that contains DNA segments known as “clustered regularly interspaced short palindromic repeats.” The system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions more efficiently than other gene-editing techniques, such as TALEN, which is short for “transcription activator-like effector nuclease.”

Despite CRISPR’s advantages, a recent study suggested it might also produce a large number of off-target effects in human cancer cell lines; specifically, modification of genes that researchers didn’t mean to change.

To see if this unwanted effect occurred in other human cell types, Dr Ye and his colleagues pitted CRISPR against TALEN in human iPSCs. The researchers compared the ability of both techniques to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another.

As model genes, the researchers used JAK2, a gene that, when mutated, causes myeloproliferative neoplasms; SERPINA1, a gene that, when mutated, causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that’s been recently discovered to be a “safe harbor” in the human genome for inserting foreign genes.

The comparison showed that, when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all 3 gene systems, inducing up to 100 times more cuts.

However, when using these genome-editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs.

Contrary to results of the human cancer cell line study, both CRISPR and TALEN had the same targeting specificity in human iPSCs, hitting only the genes they were designed to affect.

The researchers also found that the CRISPR system has a second advantage over TALEN. It can be designed to target only the mutation-containing gene without affecting the healthy gene in patients where only one copy of a gene is affected.

These findings, according to the researchers, offer reassurance that CRISPR will be a useful tool for editing the genes of human iPSCs with little risk of off-target effects.

Colony of iPSCs

Credit: Salk Institute

The gene-editing technology CRISPR can precisely and efficiently alter human stem cells, according to research published in Molecular Therapy.

Using JAK2 and other genes as models, researchers showed that CRISPR offers advantages over TALEN, another gene-editing technique, for manipulating induced pluripotent stem cells (iPSCs).

And, unlike in a previous study, CRISPR did not produce any off-target effects.

The team believes their findings could streamline and speed up efforts to modify human iPSCs for use as treatments or in the development of model systems to study diseases and test drugs.

“Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs for human therapy aren’t that far away,” said study author Zhaohui Ye, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells.”

CRISPR originated from a microbial immune system that contains DNA segments known as “clustered regularly interspaced short palindromic repeats.” The system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions more efficiently than other gene-editing techniques, such as TALEN, which is short for “transcription activator-like effector nuclease.”

Despite CRISPR’s advantages, a recent study suggested it might also produce a large number of off-target effects in human cancer cell lines; specifically, modification of genes that researchers didn’t mean to change.

To see if this unwanted effect occurred in other human cell types, Dr Ye and his colleagues pitted CRISPR against TALEN in human iPSCs. The researchers compared the ability of both techniques to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another.

As model genes, the researchers used JAK2, a gene that, when mutated, causes myeloproliferative neoplasms; SERPINA1, a gene that, when mutated, causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that’s been recently discovered to be a “safe harbor” in the human genome for inserting foreign genes.

The comparison showed that, when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all 3 gene systems, inducing up to 100 times more cuts.

However, when using these genome-editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs.

Contrary to results of the human cancer cell line study, both CRISPR and TALEN had the same targeting specificity in human iPSCs, hitting only the genes they were designed to affect.

The researchers also found that the CRISPR system has a second advantage over TALEN. It can be designed to target only the mutation-containing gene without affecting the healthy gene in patients where only one copy of a gene is affected.

These findings, according to the researchers, offer reassurance that CRISPR will be a useful tool for editing the genes of human iPSCs with little risk of off-target effects.

Colony of iPSCs

Credit: Salk Institute

The gene-editing technology CRISPR can precisely and efficiently alter human stem cells, according to research published in Molecular Therapy.

Using JAK2 and other genes as models, researchers showed that CRISPR offers advantages over TALEN, another gene-editing technique, for manipulating induced pluripotent stem cells (iPSCs).

And, unlike in a previous study, CRISPR did not produce any off-target effects.

The team believes their findings could streamline and speed up efforts to modify human iPSCs for use as treatments or in the development of model systems to study diseases and test drugs.

“Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs for human therapy aren’t that far away,” said study author Zhaohui Ye, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells.”

CRISPR originated from a microbial immune system that contains DNA segments known as “clustered regularly interspaced short palindromic repeats.” The system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions more efficiently than other gene-editing techniques, such as TALEN, which is short for “transcription activator-like effector nuclease.”

Despite CRISPR’s advantages, a recent study suggested it might also produce a large number of off-target effects in human cancer cell lines; specifically, modification of genes that researchers didn’t mean to change.

To see if this unwanted effect occurred in other human cell types, Dr Ye and his colleagues pitted CRISPR against TALEN in human iPSCs. The researchers compared the ability of both techniques to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another.

As model genes, the researchers used JAK2, a gene that, when mutated, causes myeloproliferative neoplasms; SERPINA1, a gene that, when mutated, causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that’s been recently discovered to be a “safe harbor” in the human genome for inserting foreign genes.

The comparison showed that, when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all 3 gene systems, inducing up to 100 times more cuts.

However, when using these genome-editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs.

Contrary to results of the human cancer cell line study, both CRISPR and TALEN had the same targeting specificity in human iPSCs, hitting only the genes they were designed to affect.

The researchers also found that the CRISPR system has a second advantage over TALEN. It can be designed to target only the mutation-containing gene without affecting the healthy gene in patients where only one copy of a gene is affected.

These findings, according to the researchers, offer reassurance that CRISPR will be a useful tool for editing the genes of human iPSCs with little risk of off-target effects.

Artemisia annua, from which

artemisinin is derived

Credit: Jorge Ferreira

Preclinical research suggests that using the whole plant Artemesia annua, from which the drug artemisinin is extracted, may treat malaria more effectively than artemisinin itself.

Whole-plant treatment withstood the evolution of resistance and remained effective for up to 3 times longer than pure artemisinin.

Whole-plant therapy was also more effective in killing rodent parasites that have previously evolved resistance to pure artemisinin.

Stephen Rich, PhD, of the University of Massachusetts Amherst, and his colleagues reported these findings in PNAS.

The team previously showed that the whole-plant approach is more effective at killing rodent malaria than purified artemisinin.

In the present study, the investigators conducted a series of experiments to determine the rates at which parasites become resistant to whole-plant treatment compared to the rate with pure artemisinin, and if the whole-plant treatment can overcome resistance to pharmaceutical artemisinin.

The team chose 2 rodent malaria species for particular characteristics. They chose Plasmodium yoelii because an artemisinin-resistant strain exists and could be used to test whether the whole plant can overcome that resistance.

And they chose Plasmodium chabaudi because, among several species of rodent malaria, it most closely biologically resembles the deadliest of the 5 human malaria parasites, Plasmodium falciparum.

“Conducting these experiments in different rodent malaria species also provides a robust test of the therapy,” Dr Rich noted.

To determine the respective evolutionary rates of resistance to whole-plant therapy and artemisinin, Dr Rich and his colleagues conducted artificial evolution experiments. The goal was to compare the rates at which resistance to these two treatments arises in serial passage among wild-type parasite lines.

In this technique, parasite proliferation rates determine resistance. Resistant parasites are expected to reach a certain target level at the same time, whether treatment is present or absent. Sensitive parasite strains will grow more slowly in the presence of treatment and reach the target later than untreated strains.

The investigators found that artemisinin-treated parasites achieved stable resistance to low-dose (100 mg/kg) therapy on passage 16. Those parasites were then treated with a doubled artemisinin dose, and they became resistant to this after an additional 24 passages.

By comparison, parasites did not become resistant to even the low dose of whole-plant therapy (100 mg/kg) after 49 passages.

From this, the investigators concluded that the whole-plant therapy lasts at least 3 times longer than its artemisinin counterpart, and at least twice as long as the doubled dose of pure artemisinin.

“This is especially important given the recent reports of resistance to artemisinin in malaria-endemic regions of the world,” Dr Rich said.

He and his colleagues also tested whether dried, whole-plant therapy can overcome existing resistance to pharmaceutical artemisinin.

They fed groups of mice infected with artemisinin-resistant malaria either the whole-plant therapy or artemisinin mixed with water. Single treatments were given in low (40 mg) and high (200 mg) doses. Control groups received a mouse chow placebo.

The investigators then measured the parasite levels in the rodents’ bloodstream at 9 points after treatment began.

Mice given either the low or high dose of whole-plant therapy showed a significantly greater reduction in parasitemia than those in their respective artemisinin groups. As expected for these resistant parasites, parasitemia in mice in the low-dose artemisinin group did not differ from controls.

The investigators said consuming the whole plant may be more effective than the single purified drug because the whole plant “may constitute a naturally occurring combination therapy that augments artemisinin delivery and synergizes the drug’s activity.”

Dr Rich did note that the exact mechanisms of whole-plant therapy’s effectiveness still need to be identified. But he also said the antimalarial activity of whole-plant therapy against artemisinin-resistant parasites provides “compelling reasons to further explore the role of non-pharmaceutical forms of artemisinin to treat human malaria.”

Artemisia annua, from which

artemisinin is derived

Credit: Jorge Ferreira

Preclinical research suggests that using the whole plant Artemesia annua, from which the drug artemisinin is extracted, may treat malaria more effectively than artemisinin itself.

Whole-plant treatment withstood the evolution of resistance and remained effective for up to 3 times longer than pure artemisinin.

Whole-plant therapy was also more effective in killing rodent parasites that have previously evolved resistance to pure artemisinin.

Stephen Rich, PhD, of the University of Massachusetts Amherst, and his colleagues reported these findings in PNAS.

The team previously showed that the whole-plant approach is more effective at killing rodent malaria than purified artemisinin.

In the present study, the investigators conducted a series of experiments to determine the rates at which parasites become resistant to whole-plant treatment compared to the rate with pure artemisinin, and if the whole-plant treatment can overcome resistance to pharmaceutical artemisinin.

The team chose 2 rodent malaria species for particular characteristics. They chose Plasmodium yoelii because an artemisinin-resistant strain exists and could be used to test whether the whole plant can overcome that resistance.

And they chose Plasmodium chabaudi because, among several species of rodent malaria, it most closely biologically resembles the deadliest of the 5 human malaria parasites, Plasmodium falciparum.

“Conducting these experiments in different rodent malaria species also provides a robust test of the therapy,” Dr Rich noted.

To determine the respective evolutionary rates of resistance to whole-plant therapy and artemisinin, Dr Rich and his colleagues conducted artificial evolution experiments. The goal was to compare the rates at which resistance to these two treatments arises in serial passage among wild-type parasite lines.

In this technique, parasite proliferation rates determine resistance. Resistant parasites are expected to reach a certain target level at the same time, whether treatment is present or absent. Sensitive parasite strains will grow more slowly in the presence of treatment and reach the target later than untreated strains.

The investigators found that artemisinin-treated parasites achieved stable resistance to low-dose (100 mg/kg) therapy on passage 16. Those parasites were then treated with a doubled artemisinin dose, and they became resistant to this after an additional 24 passages.

By comparison, parasites did not become resistant to even the low dose of whole-plant therapy (100 mg/kg) after 49 passages.

From this, the investigators concluded that the whole-plant therapy lasts at least 3 times longer than its artemisinin counterpart, and at least twice as long as the doubled dose of pure artemisinin.

“This is especially important given the recent reports of resistance to artemisinin in malaria-endemic regions of the world,” Dr Rich said.

He and his colleagues also tested whether dried, whole-plant therapy can overcome existing resistance to pharmaceutical artemisinin.

They fed groups of mice infected with artemisinin-resistant malaria either the whole-plant therapy or artemisinin mixed with water. Single treatments were given in low (40 mg) and high (200 mg) doses. Control groups received a mouse chow placebo.

The investigators then measured the parasite levels in the rodents’ bloodstream at 9 points after treatment began.

Mice given either the low or high dose of whole-plant therapy showed a significantly greater reduction in parasitemia than those in their respective artemisinin groups. As expected for these resistant parasites, parasitemia in mice in the low-dose artemisinin group did not differ from controls.

The investigators said consuming the whole plant may be more effective than the single purified drug because the whole plant “may constitute a naturally occurring combination therapy that augments artemisinin delivery and synergizes the drug’s activity.”

Dr Rich did note that the exact mechanisms of whole-plant therapy’s effectiveness still need to be identified. But he also said the antimalarial activity of whole-plant therapy against artemisinin-resistant parasites provides “compelling reasons to further explore the role of non-pharmaceutical forms of artemisinin to treat human malaria.”

Artemisia annua, from which

artemisinin is derived

Credit: Jorge Ferreira

Preclinical research suggests that using the whole plant Artemesia annua, from which the drug artemisinin is extracted, may treat malaria more effectively than artemisinin itself.

Whole-plant treatment withstood the evolution of resistance and remained effective for up to 3 times longer than pure artemisinin.

Whole-plant therapy was also more effective in killing rodent parasites that have previously evolved resistance to pure artemisinin.

Stephen Rich, PhD, of the University of Massachusetts Amherst, and his colleagues reported these findings in PNAS.

The team previously showed that the whole-plant approach is more effective at killing rodent malaria than purified artemisinin.

In the present study, the investigators conducted a series of experiments to determine the rates at which parasites become resistant to whole-plant treatment compared to the rate with pure artemisinin, and if the whole-plant treatment can overcome resistance to pharmaceutical artemisinin.

The team chose 2 rodent malaria species for particular characteristics. They chose Plasmodium yoelii because an artemisinin-resistant strain exists and could be used to test whether the whole plant can overcome that resistance.

And they chose Plasmodium chabaudi because, among several species of rodent malaria, it most closely biologically resembles the deadliest of the 5 human malaria parasites, Plasmodium falciparum.

“Conducting these experiments in different rodent malaria species also provides a robust test of the therapy,” Dr Rich noted.

To determine the respective evolutionary rates of resistance to whole-plant therapy and artemisinin, Dr Rich and his colleagues conducted artificial evolution experiments. The goal was to compare the rates at which resistance to these two treatments arises in serial passage among wild-type parasite lines.

In this technique, parasite proliferation rates determine resistance. Resistant parasites are expected to reach a certain target level at the same time, whether treatment is present or absent. Sensitive parasite strains will grow more slowly in the presence of treatment and reach the target later than untreated strains.

The investigators found that artemisinin-treated parasites achieved stable resistance to low-dose (100 mg/kg) therapy on passage 16. Those parasites were then treated with a doubled artemisinin dose, and they became resistant to this after an additional 24 passages.

By comparison, parasites did not become resistant to even the low dose of whole-plant therapy (100 mg/kg) after 49 passages.

From this, the investigators concluded that the whole-plant therapy lasts at least 3 times longer than its artemisinin counterpart, and at least twice as long as the doubled dose of pure artemisinin.

“This is especially important given the recent reports of resistance to artemisinin in malaria-endemic regions of the world,” Dr Rich said.

He and his colleagues also tested whether dried, whole-plant therapy can overcome existing resistance to pharmaceutical artemisinin.

They fed groups of mice infected with artemisinin-resistant malaria either the whole-plant therapy or artemisinin mixed with water. Single treatments were given in low (40 mg) and high (200 mg) doses. Control groups received a mouse chow placebo.

The investigators then measured the parasite levels in the rodents’ bloodstream at 9 points after treatment began.

Mice given either the low or high dose of whole-plant therapy showed a significantly greater reduction in parasitemia than those in their respective artemisinin groups. As expected for these resistant parasites, parasitemia in mice in the low-dose artemisinin group did not differ from controls.

The investigators said consuming the whole plant may be more effective than the single purified drug because the whole plant “may constitute a naturally occurring combination therapy that augments artemisinin delivery and synergizes the drug’s activity.”

Dr Rich did note that the exact mechanisms of whole-plant therapy’s effectiveness still need to be identified. But he also said the antimalarial activity of whole-plant therapy against artemisinin-resistant parasites provides “compelling reasons to further explore the role of non-pharmaceutical forms of artemisinin to treat human malaria.”