P falciparum in a red blood cell

Credit: St Jude Children’s

Research Hospital

An infrared spectroscopy technique can detect malaria parasites at early stages of development, according to preclinical research published in Analytical Chemistry.

A group of biochemists found this method could detect Plasmodium falciparum in red blood cells by picking up on a fatty acid signature.

This allowed the researchers to identify and quantify parasites at various stages of development, including the ring and gametocyte stages.

The team also pointed out that the spectrometer they used is portable, inexpensive, and does not require highly trained staff for operation. It could therefore prove useful in the field.

“Current tests for malaria suffer from serious limitations,” said study author Bayden Wood, PhD, of Monash University in Victoria, Australia.

“Many are expensive [and] require specialist instruments and highly trained staff to judge whether blood samples contain the parasite. What’s been holding us back is the lack of an accurate and inexpensive test to detect malaria early and stop it in its tracks. We believe we’ve found it.”

Dr Wood and his colleagues already knew that fatty acids were a marker for malaria from previous studies conducted at the Australian Synchrotron. The Synchrotron allowed the team to see the different life stages of the parasite and the variation in its fatty acids.

The researchers thought they might be able to use this information for diagnosis, but they needed a more portable detection method.

So they decided to test whether attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) could detect the fatty acid signature. The technique utilizes infrared light to pick up on the vibrations of molecules.

The researchers spiked red blood cells with parasites of different numbers and life stages and observed them using ATR-FT-IR.

Dr Wood said the method produced results within minutes. And it gave a clear indication of malaria at a much earlier stage of infection than current tests on the market—at the ring and gametocyte stages.

The absolute detection limit was 0.00001% parasitemia (<1 parasite/μL of blood) for cultured early ring-stage parasites in a suspension of normal red blood cells.

“Now that we can detect the early stages of a parasite’s life in the bloodstream, the disease will be much easier to test and treat,” Dr Wood said. “The big advantage of our test is that it doesn’t need scientists and expensive equipment. This has the potential to dramatically reduce the number of people dying from this disease in remote communities.”

The method also shows the potential to detect a number of other blood-borne diseases, according to the researchers. Dr Wood and his colleagues are now planning a clinical trial of ATR-FT-IR in Thailand.

P falciparum in a red blood cell

Credit: St Jude Children’s

Research Hospital

An infrared spectroscopy technique can detect malaria parasites at early stages of development, according to preclinical research published in Analytical Chemistry.

A group of biochemists found this method could detect Plasmodium falciparum in red blood cells by picking up on a fatty acid signature.

This allowed the researchers to identify and quantify parasites at various stages of development, including the ring and gametocyte stages.

The team also pointed out that the spectrometer they used is portable, inexpensive, and does not require highly trained staff for operation. It could therefore prove useful in the field.

“Current tests for malaria suffer from serious limitations,” said study author Bayden Wood, PhD, of Monash University in Victoria, Australia.

“Many are expensive [and] require specialist instruments and highly trained staff to judge whether blood samples contain the parasite. What’s been holding us back is the lack of an accurate and inexpensive test to detect malaria early and stop it in its tracks. We believe we’ve found it.”

Dr Wood and his colleagues already knew that fatty acids were a marker for malaria from previous studies conducted at the Australian Synchrotron. The Synchrotron allowed the team to see the different life stages of the parasite and the variation in its fatty acids.

The researchers thought they might be able to use this information for diagnosis, but they needed a more portable detection method.

So they decided to test whether attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) could detect the fatty acid signature. The technique utilizes infrared light to pick up on the vibrations of molecules.

The researchers spiked red blood cells with parasites of different numbers and life stages and observed them using ATR-FT-IR.

Dr Wood said the method produced results within minutes. And it gave a clear indication of malaria at a much earlier stage of infection than current tests on the market—at the ring and gametocyte stages.

The absolute detection limit was 0.00001% parasitemia (<1 parasite/μL of blood) for cultured early ring-stage parasites in a suspension of normal red blood cells.

“Now that we can detect the early stages of a parasite’s life in the bloodstream, the disease will be much easier to test and treat,” Dr Wood said. “The big advantage of our test is that it doesn’t need scientists and expensive equipment. This has the potential to dramatically reduce the number of people dying from this disease in remote communities.”

The method also shows the potential to detect a number of other blood-borne diseases, according to the researchers. Dr Wood and his colleagues are now planning a clinical trial of ATR-FT-IR in Thailand.

P falciparum in a red blood cell

Credit: St Jude Children’s

Research Hospital

An infrared spectroscopy technique can detect malaria parasites at early stages of development, according to preclinical research published in Analytical Chemistry.

A group of biochemists found this method could detect Plasmodium falciparum in red blood cells by picking up on a fatty acid signature.

This allowed the researchers to identify and quantify parasites at various stages of development, including the ring and gametocyte stages.

The team also pointed out that the spectrometer they used is portable, inexpensive, and does not require highly trained staff for operation. It could therefore prove useful in the field.

“Current tests for malaria suffer from serious limitations,” said study author Bayden Wood, PhD, of Monash University in Victoria, Australia.

“Many are expensive [and] require specialist instruments and highly trained staff to judge whether blood samples contain the parasite. What’s been holding us back is the lack of an accurate and inexpensive test to detect malaria early and stop it in its tracks. We believe we’ve found it.”

Dr Wood and his colleagues already knew that fatty acids were a marker for malaria from previous studies conducted at the Australian Synchrotron. The Synchrotron allowed the team to see the different life stages of the parasite and the variation in its fatty acids.

The researchers thought they might be able to use this information for diagnosis, but they needed a more portable detection method.

So they decided to test whether attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) could detect the fatty acid signature. The technique utilizes infrared light to pick up on the vibrations of molecules.

The researchers spiked red blood cells with parasites of different numbers and life stages and observed them using ATR-FT-IR.

Dr Wood said the method produced results within minutes. And it gave a clear indication of malaria at a much earlier stage of infection than current tests on the market—at the ring and gametocyte stages.

The absolute detection limit was 0.00001% parasitemia (<1 parasite/μL of blood) for cultured early ring-stage parasites in a suspension of normal red blood cells.

“Now that we can detect the early stages of a parasite’s life in the bloodstream, the disease will be much easier to test and treat,” Dr Wood said. “The big advantage of our test is that it doesn’t need scientists and expensive equipment. This has the potential to dramatically reduce the number of people dying from this disease in remote communities.”

The method also shows the potential to detect a number of other blood-borne diseases, according to the researchers. Dr Wood and his colleagues are now planning a clinical trial of ATR-FT-IR in Thailand.

Blood for transfusion

Credit: Daniel Gay

Hospira, Inc., has issued a Class I recall of Abbott Acclaim infusion pumps and Hospira Acclaim Encore infusion pumps, after receiving reports of broken door assemblies on these products.

If a door assembly breaks, the door may not close properly and an over-infusion or a delay of therapy may occur.

If the door cannot be closed, the pump cannot be used, and this can result in a delay of therapy.

Use of these products may cause serious adverse events, including death.

These pumps are used to deliver hydration fluids, drugs, blood and blood fractions, intravenous nutritionals, and enteral nutritionals.

The affected Abbott Acclaim Infusion Pumps, list Number 12032, were manufactured from February 1998 to November 1998 and distributed from September 1998 through February 2004.

The affected Hospira Acclaim Encore infusion pumps, list Number 12237, were manufactured from February 1997 to February 2010 and distributed from July 1999 through November 2013.

Hospira is recommending that users inspect each Hospira/Abbott Acclaim Encore infusion pump for door handle cracks prior to programming a therapy, by taking the following steps:

1. After inserting the tubing (with the roller clamp closed) and closing the door handle against the infusion pump, check that the door is fully closed.

If a pump has a door that does not close properly and a gap or separation exists between the completely closed door and the pump itself, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT). If the door closes correctly, proceed to Step 2.

2. If the door closes correctly and a gap or separation does not exist between the completely closed door and the pump itself, check that there is no free flow activity in the drip chamber of the administration set by opening the roller clamp.

If free flow is detected, close the roller clamp, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT).

3. If no issues are found through steps 1 and 2, the pump is acceptable for use. However, healthcare professionals should still ensure that anyone in their facility who might use these products is made aware of this safety notification and the recommended actions.

Healthcare professionals and patients can report adverse events or side effects related to the use of these products to the FDA’s MedWatch Program.

Blood for transfusion

Credit: Daniel Gay

Hospira, Inc., has issued a Class I recall of Abbott Acclaim infusion pumps and Hospira Acclaim Encore infusion pumps, after receiving reports of broken door assemblies on these products.

If a door assembly breaks, the door may not close properly and an over-infusion or a delay of therapy may occur.

If the door cannot be closed, the pump cannot be used, and this can result in a delay of therapy.

Use of these products may cause serious adverse events, including death.

These pumps are used to deliver hydration fluids, drugs, blood and blood fractions, intravenous nutritionals, and enteral nutritionals.

The affected Abbott Acclaim Infusion Pumps, list Number 12032, were manufactured from February 1998 to November 1998 and distributed from September 1998 through February 2004.

The affected Hospira Acclaim Encore infusion pumps, list Number 12237, were manufactured from February 1997 to February 2010 and distributed from July 1999 through November 2013.

Hospira is recommending that users inspect each Hospira/Abbott Acclaim Encore infusion pump for door handle cracks prior to programming a therapy, by taking the following steps:

1. After inserting the tubing (with the roller clamp closed) and closing the door handle against the infusion pump, check that the door is fully closed.

If a pump has a door that does not close properly and a gap or separation exists between the completely closed door and the pump itself, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT). If the door closes correctly, proceed to Step 2.

2. If the door closes correctly and a gap or separation does not exist between the completely closed door and the pump itself, check that there is no free flow activity in the drip chamber of the administration set by opening the roller clamp.

If free flow is detected, close the roller clamp, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT).

3. If no issues are found through steps 1 and 2, the pump is acceptable for use. However, healthcare professionals should still ensure that anyone in their facility who might use these products is made aware of this safety notification and the recommended actions.

Healthcare professionals and patients can report adverse events or side effects related to the use of these products to the FDA’s MedWatch Program.

Blood for transfusion

Credit: Daniel Gay

Hospira, Inc., has issued a Class I recall of Abbott Acclaim infusion pumps and Hospira Acclaim Encore infusion pumps, after receiving reports of broken door assemblies on these products.

If a door assembly breaks, the door may not close properly and an over-infusion or a delay of therapy may occur.

If the door cannot be closed, the pump cannot be used, and this can result in a delay of therapy.

Use of these products may cause serious adverse events, including death.

These pumps are used to deliver hydration fluids, drugs, blood and blood fractions, intravenous nutritionals, and enteral nutritionals.

The affected Abbott Acclaim Infusion Pumps, list Number 12032, were manufactured from February 1998 to November 1998 and distributed from September 1998 through February 2004.

The affected Hospira Acclaim Encore infusion pumps, list Number 12237, were manufactured from February 1997 to February 2010 and distributed from July 1999 through November 2013.

Hospira is recommending that users inspect each Hospira/Abbott Acclaim Encore infusion pump for door handle cracks prior to programming a therapy, by taking the following steps:

1. After inserting the tubing (with the roller clamp closed) and closing the door handle against the infusion pump, check that the door is fully closed.

If a pump has a door that does not close properly and a gap or separation exists between the completely closed door and the pump itself, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT). If the door closes correctly, proceed to Step 2.

2. If the door closes correctly and a gap or separation does not exist between the completely closed door and the pump itself, check that there is no free flow activity in the drip chamber of the administration set by opening the roller clamp.

If free flow is detected, close the roller clamp, remove the pump from clinical service, and call Hospira at 1-800-441-4100 (M-F, 8am-5pm, CT).

3. If no issues are found through steps 1 and 2, the pump is acceptable for use. However, healthcare professionals should still ensure that anyone in their facility who might use these products is made aware of this safety notification and the recommended actions.

Healthcare professionals and patients can report adverse events or side effects related to the use of these products to the FDA’s MedWatch Program.

Drug vials and a syringe

The US Food and Drug Administration (FDA) has expanded the approval of omacetaxine mepesuccinate (Synribo) to include home administration.

The drug is already FDA-approved to treat adults with chronic or accelerated phase chronic myeloid leukemia (CML) who do not respond to or cannot tolerate 2 or more tyrosine kinase inhibitors.

The new approval allows CML patients to self-administer subcutaneous injections of omacetaxine mepesuccinate at home.

“It had been necessary for adults living with chronic or accelerated phase CML who are prescribed Synribo to travel to their doctor’s office twice a day for 2 weeks, which can be extremely burdensome and inconvenient to both patients and their caregivers,” said Meir Wetzler, MD, FACP, Chief of the Leukemia Section at Roswell Park Cancer Institute in Buffalo, New York.

“Now, physicians can decide if their patients are candidates for self-administration and, if so, provide their patients with guidance on how to properly administer reconstituted Synribo in the home.”

The drug’s maker, Teva Pharmaceutical Industries, Ltd., is working to finalize a pharmacy support program that will help facilitate successful home administration of omacetaxine mepesuccinate. The program is expected to “go live” this month or next.

About omacetaxine mepesuccinate

Omacetaxine mepesuccinate is a protein synthesis inhibitor. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

In October 2012, the FDA granted omacetaxine mepesuccinate accelerated approval for the treatment of adult patients with chronic or accelerated phase CML with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. Omacetaxine mepesuccinate gained full FDA approval in February.

The drug has been associated with severe and fatal myelosuppression, including thrombocytopenia, neutropenia, and anemia in some patients. So healthcare professionals should monitor patients’ complete blood counts weekly during induction and initial maintenance cycles and every 2 weeks during later maintenance cycles, as clinically indicated.

Omacetaxine mepesuccinate has been known to cause severe thrombocytopenia, which increases the risk of hemorrhage. Fatalities from cerebral hemorrhage have occurred. And severe, non-fatal gastrointestinal hemorrhages have occurred.

So healthcare professionals should monitor platelet counts as part of the complete blood count as recommended. Patients should not receive anticoagulants, aspirin, or non-steroidal anti-inflammatory drugs when their platelet counts are <50,000/μL, as these drugs may increase the risk of bleeding.

Omacetaxine mepesuccinate can induce glucose intolerance as well. So healthcare professionals should monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Patients with poorly controlled diabetes mellitus should not receive omacetaxine mepesuccinate until good glycemic control has been established.

Omacetaxine mepesuccinate can cause fetal harm when administered to a pregnant woman. So women should be advised to avoid becoming pregnant while using the drug.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug vials and a syringe

The US Food and Drug Administration (FDA) has expanded the approval of omacetaxine mepesuccinate (Synribo) to include home administration.

The drug is already FDA-approved to treat adults with chronic or accelerated phase chronic myeloid leukemia (CML) who do not respond to or cannot tolerate 2 or more tyrosine kinase inhibitors.

The new approval allows CML patients to self-administer subcutaneous injections of omacetaxine mepesuccinate at home.

“It had been necessary for adults living with chronic or accelerated phase CML who are prescribed Synribo to travel to their doctor’s office twice a day for 2 weeks, which can be extremely burdensome and inconvenient to both patients and their caregivers,” said Meir Wetzler, MD, FACP, Chief of the Leukemia Section at Roswell Park Cancer Institute in Buffalo, New York.

“Now, physicians can decide if their patients are candidates for self-administration and, if so, provide their patients with guidance on how to properly administer reconstituted Synribo in the home.”

The drug’s maker, Teva Pharmaceutical Industries, Ltd., is working to finalize a pharmacy support program that will help facilitate successful home administration of omacetaxine mepesuccinate. The program is expected to “go live” this month or next.

About omacetaxine mepesuccinate

Omacetaxine mepesuccinate is a protein synthesis inhibitor. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

In October 2012, the FDA granted omacetaxine mepesuccinate accelerated approval for the treatment of adult patients with chronic or accelerated phase CML with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. Omacetaxine mepesuccinate gained full FDA approval in February.

The drug has been associated with severe and fatal myelosuppression, including thrombocytopenia, neutropenia, and anemia in some patients. So healthcare professionals should monitor patients’ complete blood counts weekly during induction and initial maintenance cycles and every 2 weeks during later maintenance cycles, as clinically indicated.

Omacetaxine mepesuccinate has been known to cause severe thrombocytopenia, which increases the risk of hemorrhage. Fatalities from cerebral hemorrhage have occurred. And severe, non-fatal gastrointestinal hemorrhages have occurred.

So healthcare professionals should monitor platelet counts as part of the complete blood count as recommended. Patients should not receive anticoagulants, aspirin, or non-steroidal anti-inflammatory drugs when their platelet counts are <50,000/μL, as these drugs may increase the risk of bleeding.

Omacetaxine mepesuccinate can induce glucose intolerance as well. So healthcare professionals should monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Patients with poorly controlled diabetes mellitus should not receive omacetaxine mepesuccinate until good glycemic control has been established.

Omacetaxine mepesuccinate can cause fetal harm when administered to a pregnant woman. So women should be advised to avoid becoming pregnant while using the drug.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug vials and a syringe

The US Food and Drug Administration (FDA) has expanded the approval of omacetaxine mepesuccinate (Synribo) to include home administration.

The drug is already FDA-approved to treat adults with chronic or accelerated phase chronic myeloid leukemia (CML) who do not respond to or cannot tolerate 2 or more tyrosine kinase inhibitors.

The new approval allows CML patients to self-administer subcutaneous injections of omacetaxine mepesuccinate at home.

“It had been necessary for adults living with chronic or accelerated phase CML who are prescribed Synribo to travel to their doctor’s office twice a day for 2 weeks, which can be extremely burdensome and inconvenient to both patients and their caregivers,” said Meir Wetzler, MD, FACP, Chief of the Leukemia Section at Roswell Park Cancer Institute in Buffalo, New York.

“Now, physicians can decide if their patients are candidates for self-administration and, if so, provide their patients with guidance on how to properly administer reconstituted Synribo in the home.”

The drug’s maker, Teva Pharmaceutical Industries, Ltd., is working to finalize a pharmacy support program that will help facilitate successful home administration of omacetaxine mepesuccinate. The program is expected to “go live” this month or next.

About omacetaxine mepesuccinate

Omacetaxine mepesuccinate is a protein synthesis inhibitor. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

In October 2012, the FDA granted omacetaxine mepesuccinate accelerated approval for the treatment of adult patients with chronic or accelerated phase CML with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. Omacetaxine mepesuccinate gained full FDA approval in February.

The drug has been associated with severe and fatal myelosuppression, including thrombocytopenia, neutropenia, and anemia in some patients. So healthcare professionals should monitor patients’ complete blood counts weekly during induction and initial maintenance cycles and every 2 weeks during later maintenance cycles, as clinically indicated.

Omacetaxine mepesuccinate has been known to cause severe thrombocytopenia, which increases the risk of hemorrhage. Fatalities from cerebral hemorrhage have occurred. And severe, non-fatal gastrointestinal hemorrhages have occurred.

So healthcare professionals should monitor platelet counts as part of the complete blood count as recommended. Patients should not receive anticoagulants, aspirin, or non-steroidal anti-inflammatory drugs when their platelet counts are <50,000/μL, as these drugs may increase the risk of bleeding.

Omacetaxine mepesuccinate can induce glucose intolerance as well. So healthcare professionals should monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Patients with poorly controlled diabetes mellitus should not receive omacetaxine mepesuccinate until good glycemic control has been established.

Omacetaxine mepesuccinate can cause fetal harm when administered to a pregnant woman. So women should be advised to avoid becoming pregnant while using the drug.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Click here to listen to more of our interview with Dr. Mourad

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Click here to listen to more of our interview with Dr. Gottlieb.

Click here to listen to more of our interview with Dr. Gottlieb.

Click here to listen to more of our interview with Dr. Gottlieb.

7:00 a.m. When they called me for this consult on this young female with known lupus presenting with pleuritic chest pain, they didn’t tell me that (a) she has a history of pleural effusions, and (b) her creatinine is 4.9 mg/dL.

8:00 a.m. Waiting for my patient to be roomed. We’re implementing a new electronic health record, so I have to wait for the medical assistant (MA) to finish her tasks: input the patient’s medications, take his vital signs, and ask for his chief complaint.

8:20 a.m. Patient is still not ready for me. Who thought it would be a good idea for the MA to take the patient’s medications? It’d be so much more efficient if I did it myself.

9:00 a.m. Finally finished with the first patient. It was a follow-up visit that was scheduled as 15 minutes. I am now 45 minutes behind schedule. Thankfully, the MA managed to use the 45 minutes to room the 8:15 patient.

12:30 p.m. Whew, I just finished my morning. I start again in 30 minutes. I am never going to finish these 12 charts in 30 minutes. Also, I am hungry. If I don’t eat now, I am going to have my MA for lunch.

12:45 p.m. Speaking to Dr. Winchester from Blue Cross to get approval for a contrast MRI of the right foot. (This call may be recorded. What did your x-rays show? Have you failed conservative treatment? Will it change management? Here’s your approval number.)

1:00 p.m. The new patient is here. She is the proud owner of a very long med list. It’ll probably take the MA 30 minutes to get through all that. Let me call dermatology in the meantime; I need a full-thickness skin biopsy on Mrs. Rodrigues. (One week later, biopsy shows polyarteritis nodosa.)

3:15 p.m. I just finished a visit with Silvi. Her rheumatoid arthritis is quiescent, but she is in tears. Not only did her mother die unexpectedly from a ruptured aneurysm 2 months ago, she has just received a new diagnosis of breast cancer, and her husband lost his job. I can’t make this stuff up. That was an emotionally draining visit. I need a drink. Oh wait, there are no drinks to be had at a doctor’s office. Maybe the drug rep brought some ice cream.

3:20 p.m. Some ice cream regret going on here.

4:40 p.m. Just got done with a new-patient consultation for a "positive" antinuclear antibody test of 1:40 and a positive systems review. I’m exhausted.

6:15 p.m. Returning phone calls. Mrs. Greggerson is regaling me with details of her ablutions.

6:35 p.m. Filling out prior authorization forms for a biologic. Among the questions: A_1c, T score, growth velocity, Mini-Mental State Exam, free and total testosterone, hepatitis C viral load and genotype. I would like to officially nominate this form for Most Number of Irrelevant Questions Ever.

7:00 p.m. Finally, last prior-authorization form for the day. Wait ... it’s for methotrexate? Since when have I needed to get prior authorization for methotrexate? I didn’t think it was even possible for me to get any angrier after the Mini-Mental State question.

8:00 p.m. Finally home. I’m too beat to go to the gym. My good decision–making reserves are exhausted. I would rather have a glass of red. The resveratrol will do me more good than a workout.

Dr. Chan practices rheumatology in Pawtucket, R.I.

7:00 a.m. When they called me for this consult on this young female with known lupus presenting with pleuritic chest pain, they didn’t tell me that (a) she has a history of pleural effusions, and (b) her creatinine is 4.9 mg/dL.

8:00 a.m. Waiting for my patient to be roomed. We’re implementing a new electronic health record, so I have to wait for the medical assistant (MA) to finish her tasks: input the patient’s medications, take his vital signs, and ask for his chief complaint.

8:20 a.m. Patient is still not ready for me. Who thought it would be a good idea for the MA to take the patient’s medications? It’d be so much more efficient if I did it myself.

9:00 a.m. Finally finished with the first patient. It was a follow-up visit that was scheduled as 15 minutes. I am now 45 minutes behind schedule. Thankfully, the MA managed to use the 45 minutes to room the 8:15 patient.

12:30 p.m. Whew, I just finished my morning. I start again in 30 minutes. I am never going to finish these 12 charts in 30 minutes. Also, I am hungry. If I don’t eat now, I am going to have my MA for lunch.

12:45 p.m. Speaking to Dr. Winchester from Blue Cross to get approval for a contrast MRI of the right foot. (This call may be recorded. What did your x-rays show? Have you failed conservative treatment? Will it change management? Here’s your approval number.)

1:00 p.m. The new patient is here. She is the proud owner of a very long med list. It’ll probably take the MA 30 minutes to get through all that. Let me call dermatology in the meantime; I need a full-thickness skin biopsy on Mrs. Rodrigues. (One week later, biopsy shows polyarteritis nodosa.)

3:15 p.m. I just finished a visit with Silvi. Her rheumatoid arthritis is quiescent, but she is in tears. Not only did her mother die unexpectedly from a ruptured aneurysm 2 months ago, she has just received a new diagnosis of breast cancer, and her husband lost his job. I can’t make this stuff up. That was an emotionally draining visit. I need a drink. Oh wait, there are no drinks to be had at a doctor’s office. Maybe the drug rep brought some ice cream.

3:20 p.m. Some ice cream regret going on here.

4:40 p.m. Just got done with a new-patient consultation for a "positive" antinuclear antibody test of 1:40 and a positive systems review. I’m exhausted.

6:15 p.m. Returning phone calls. Mrs. Greggerson is regaling me with details of her ablutions.

6:35 p.m. Filling out prior authorization forms for a biologic. Among the questions: A_1c, T score, growth velocity, Mini-Mental State Exam, free and total testosterone, hepatitis C viral load and genotype. I would like to officially nominate this form for Most Number of Irrelevant Questions Ever.

7:00 p.m. Finally, last prior-authorization form for the day. Wait ... it’s for methotrexate? Since when have I needed to get prior authorization for methotrexate? I didn’t think it was even possible for me to get any angrier after the Mini-Mental State question.

8:00 p.m. Finally home. I’m too beat to go to the gym. My good decision–making reserves are exhausted. I would rather have a glass of red. The resveratrol will do me more good than a workout.

Dr. Chan practices rheumatology in Pawtucket, R.I.

7:00 a.m. When they called me for this consult on this young female with known lupus presenting with pleuritic chest pain, they didn’t tell me that (a) she has a history of pleural effusions, and (b) her creatinine is 4.9 mg/dL.

8:00 a.m. Waiting for my patient to be roomed. We’re implementing a new electronic health record, so I have to wait for the medical assistant (MA) to finish her tasks: input the patient’s medications, take his vital signs, and ask for his chief complaint.

8:20 a.m. Patient is still not ready for me. Who thought it would be a good idea for the MA to take the patient’s medications? It’d be so much more efficient if I did it myself.

9:00 a.m. Finally finished with the first patient. It was a follow-up visit that was scheduled as 15 minutes. I am now 45 minutes behind schedule. Thankfully, the MA managed to use the 45 minutes to room the 8:15 patient.

12:30 p.m. Whew, I just finished my morning. I start again in 30 minutes. I am never going to finish these 12 charts in 30 minutes. Also, I am hungry. If I don’t eat now, I am going to have my MA for lunch.

12:45 p.m. Speaking to Dr. Winchester from Blue Cross to get approval for a contrast MRI of the right foot. (This call may be recorded. What did your x-rays show? Have you failed conservative treatment? Will it change management? Here’s your approval number.)

1:00 p.m. The new patient is here. She is the proud owner of a very long med list. It’ll probably take the MA 30 minutes to get through all that. Let me call dermatology in the meantime; I need a full-thickness skin biopsy on Mrs. Rodrigues. (One week later, biopsy shows polyarteritis nodosa.)

3:15 p.m. I just finished a visit with Silvi. Her rheumatoid arthritis is quiescent, but she is in tears. Not only did her mother die unexpectedly from a ruptured aneurysm 2 months ago, she has just received a new diagnosis of breast cancer, and her husband lost his job. I can’t make this stuff up. That was an emotionally draining visit. I need a drink. Oh wait, there are no drinks to be had at a doctor’s office. Maybe the drug rep brought some ice cream.

3:20 p.m. Some ice cream regret going on here.

4:40 p.m. Just got done with a new-patient consultation for a "positive" antinuclear antibody test of 1:40 and a positive systems review. I’m exhausted.

6:15 p.m. Returning phone calls. Mrs. Greggerson is regaling me with details of her ablutions.

6:35 p.m. Filling out prior authorization forms for a biologic. Among the questions: A_1c, T score, growth velocity, Mini-Mental State Exam, free and total testosterone, hepatitis C viral load and genotype. I would like to officially nominate this form for Most Number of Irrelevant Questions Ever.

7:00 p.m. Finally, last prior-authorization form for the day. Wait ... it’s for methotrexate? Since when have I needed to get prior authorization for methotrexate? I didn’t think it was even possible for me to get any angrier after the Mini-Mental State question.

8:00 p.m. Finally home. I’m too beat to go to the gym. My good decision–making reserves are exhausted. I would rather have a glass of red. The resveratrol will do me more good than a workout.

Dr. Chan practices rheumatology in Pawtucket, R.I.

Like many of you, I’m currently in New York City for 5 days of psychiatry and psychiatrists, 24/7. I’m hoping there will be a bagel with lox in there somewhere as well.

I wanted to talk about one section of Rep. Tim Murphy’s (R-Pa.) proposed legislation, H.R. 3717, the Helping Families in Mental Health Crisis Act. If you’re not familiar with it, the legislation intends to overhaul a broken mental health system in the United States. One component of the bill, Section 301 located on page 44, deals with modifying HIPAA such that mental health providers can speak with caregivers and family members. Rep. Murphy – who is also a psychologist – has noted in his television appearance and in public testimony that HIPAA is misinterpreted such that families are sometimes told they may not provide historical information about the patient. HIPAA does not actually prevent a mental health professional from listening to anyone’s free speech, but there seem to be times when the involved parties believe this is the case.

In addition, Rep. Murphy noted that HIPAA prevents clinicians from releasing information to caretakers that might help in providing for outpatient care – specifically for releasing medication information and follow-up appointments to those who may be responsible for helping patients negotiate these crucial items.

The proposed legislation reads:

"Caregiver Access to Information: ...to an individual with a serious mental illness who does not provide consent for the disclosure of protected health information to a caregiver of such individual, the caregiver shall be treated by a covered entity as a personal representative ... when the provider furnishing services to the individual reasonably believes it is necessary for protected health information of the individual to be made available to the caregiver in order to protect the health, safety, or welfare of such individuals or the safety of one or more other individuals."

The bill goes on to define "caregiver" as an immediate family member, an individual who assumes primary responsibility for providing for the patient’s basic needs, or a personal representative as determined by law. I think we all agree that collaboration and communication are essential to the care of our patients, and so I applaud these efforts. I worry, however, about the unintended consequences and what roads this might lead us down.

Long before we had HIPAA, we had requirements for patient confidentiality. I, like Rep. Murphy, believe that HIPAA gets distorted. "We need to let your family know your discharge medications and follow-up appointments," is not often met with resistance, but if it is, shouldn’t that be respected? What if patients have valid reasons for not wanting family to know their medications? What if they feel their family is too intrusive, or is part of the problem? Such legislation might suggest that the family is always right and the patient is always wrong.

While the intent (as I’ve understood it from Rep. Murphy’s speeches) is to allow hospitals to tell families, "Yes, your loved [one] has been admitted to our inpatient unit," or to allow well-negotiated follow-up to prevent relapse, might such legislation lead patients to believe that the content of their discussions with mental health professionals can be relayed to others against their will? Might it serve as one more reason for a troubled individual to avoid care?

From a psychiatrist’s point of view, I might be concerned that I would agree with a patient that information should not be released to family, and nothing about this law would then force me to release it. But would family members feel the law says otherwise? Will they contend, "My family member is mentally ill so HIPAA does not apply, and you must release information to me?" While any given psychiatrist might choose not to release information on any given patient, I wonder if this might be setting us up to be at odds with families, and that would not be a good thing. Much as I’m no fan of HIPAA for many reasons, people do understand the concept that confidentiality is required by law. Perhaps I’m reading too much into this?

Finally, we all agree that eliminating stigma is a good thing when it comes to facilitating voluntary care for those who might need it. But I wonder if we can say that people with mental illnesses are just like everyone else, that this is a medical condition just like other conditions, but for this select group of people they lose their right to privacy, much as children have no right to medical privacy. Might that add to the stigma of mental illness?

I don’t have an answer. I believe the intentions of the Helping Families in Mental Health Crisis Act are good, and I believe they target weaknesses in our system. But I also worry that the legislation might create as many problems as it might fix.

The comments feature of the Clinical Psychiatry News website is turned off for the moment, and I would love to hear your thoughts. Please do e-mail with your comments; I can be reached at [email protected], or you may comment on a similar post here.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

Like many of you, I’m currently in New York City for 5 days of psychiatry and psychiatrists, 24/7. I’m hoping there will be a bagel with lox in there somewhere as well.

I wanted to talk about one section of Rep. Tim Murphy’s (R-Pa.) proposed legislation, H.R. 3717, the Helping Families in Mental Health Crisis Act. If you’re not familiar with it, the legislation intends to overhaul a broken mental health system in the United States. One component of the bill, Section 301 located on page 44, deals with modifying HIPAA such that mental health providers can speak with caregivers and family members. Rep. Murphy – who is also a psychologist – has noted in his television appearance and in public testimony that HIPAA is misinterpreted such that families are sometimes told they may not provide historical information about the patient. HIPAA does not actually prevent a mental health professional from listening to anyone’s free speech, but there seem to be times when the involved parties believe this is the case.

In addition, Rep. Murphy noted that HIPAA prevents clinicians from releasing information to caretakers that might help in providing for outpatient care – specifically for releasing medication information and follow-up appointments to those who may be responsible for helping patients negotiate these crucial items.

The proposed legislation reads:

"Caregiver Access to Information: ...to an individual with a serious mental illness who does not provide consent for the disclosure of protected health information to a caregiver of such individual, the caregiver shall be treated by a covered entity as a personal representative ... when the provider furnishing services to the individual reasonably believes it is necessary for protected health information of the individual to be made available to the caregiver in order to protect the health, safety, or welfare of such individuals or the safety of one or more other individuals."

The bill goes on to define "caregiver" as an immediate family member, an individual who assumes primary responsibility for providing for the patient’s basic needs, or a personal representative as determined by law. I think we all agree that collaboration and communication are essential to the care of our patients, and so I applaud these efforts. I worry, however, about the unintended consequences and what roads this might lead us down.

Long before we had HIPAA, we had requirements for patient confidentiality. I, like Rep. Murphy, believe that HIPAA gets distorted. "We need to let your family know your discharge medications and follow-up appointments," is not often met with resistance, but if it is, shouldn’t that be respected? What if patients have valid reasons for not wanting family to know their medications? What if they feel their family is too intrusive, or is part of the problem? Such legislation might suggest that the family is always right and the patient is always wrong.

While the intent (as I’ve understood it from Rep. Murphy’s speeches) is to allow hospitals to tell families, "Yes, your loved [one] has been admitted to our inpatient unit," or to allow well-negotiated follow-up to prevent relapse, might such legislation lead patients to believe that the content of their discussions with mental health professionals can be relayed to others against their will? Might it serve as one more reason for a troubled individual to avoid care?

From a psychiatrist’s point of view, I might be concerned that I would agree with a patient that information should not be released to family, and nothing about this law would then force me to release it. But would family members feel the law says otherwise? Will they contend, "My family member is mentally ill so HIPAA does not apply, and you must release information to me?" While any given psychiatrist might choose not to release information on any given patient, I wonder if this might be setting us up to be at odds with families, and that would not be a good thing. Much as I’m no fan of HIPAA for many reasons, people do understand the concept that confidentiality is required by law. Perhaps I’m reading too much into this?

Finally, we all agree that eliminating stigma is a good thing when it comes to facilitating voluntary care for those who might need it. But I wonder if we can say that people with mental illnesses are just like everyone else, that this is a medical condition just like other conditions, but for this select group of people they lose their right to privacy, much as children have no right to medical privacy. Might that add to the stigma of mental illness?

I don’t have an answer. I believe the intentions of the Helping Families in Mental Health Crisis Act are good, and I believe they target weaknesses in our system. But I also worry that the legislation might create as many problems as it might fix.

The comments feature of the Clinical Psychiatry News website is turned off for the moment, and I would love to hear your thoughts. Please do e-mail with your comments; I can be reached at [email protected], or you may comment on a similar post here.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

Like many of you, I’m currently in New York City for 5 days of psychiatry and psychiatrists, 24/7. I’m hoping there will be a bagel with lox in there somewhere as well.

I wanted to talk about one section of Rep. Tim Murphy’s (R-Pa.) proposed legislation, H.R. 3717, the Helping Families in Mental Health Crisis Act. If you’re not familiar with it, the legislation intends to overhaul a broken mental health system in the United States. One component of the bill, Section 301 located on page 44, deals with modifying HIPAA such that mental health providers can speak with caregivers and family members. Rep. Murphy – who is also a psychologist – has noted in his television appearance and in public testimony that HIPAA is misinterpreted such that families are sometimes told they may not provide historical information about the patient. HIPAA does not actually prevent a mental health professional from listening to anyone’s free speech, but there seem to be times when the involved parties believe this is the case.

In addition, Rep. Murphy noted that HIPAA prevents clinicians from releasing information to caretakers that might help in providing for outpatient care – specifically for releasing medication information and follow-up appointments to those who may be responsible for helping patients negotiate these crucial items.

The proposed legislation reads:

"Caregiver Access to Information: ...to an individual with a serious mental illness who does not provide consent for the disclosure of protected health information to a caregiver of such individual, the caregiver shall be treated by a covered entity as a personal representative ... when the provider furnishing services to the individual reasonably believes it is necessary for protected health information of the individual to be made available to the caregiver in order to protect the health, safety, or welfare of such individuals or the safety of one or more other individuals."

The bill goes on to define "caregiver" as an immediate family member, an individual who assumes primary responsibility for providing for the patient’s basic needs, or a personal representative as determined by law. I think we all agree that collaboration and communication are essential to the care of our patients, and so I applaud these efforts. I worry, however, about the unintended consequences and what roads this might lead us down.

Long before we had HIPAA, we had requirements for patient confidentiality. I, like Rep. Murphy, believe that HIPAA gets distorted. "We need to let your family know your discharge medications and follow-up appointments," is not often met with resistance, but if it is, shouldn’t that be respected? What if patients have valid reasons for not wanting family to know their medications? What if they feel their family is too intrusive, or is part of the problem? Such legislation might suggest that the family is always right and the patient is always wrong.

While the intent (as I’ve understood it from Rep. Murphy’s speeches) is to allow hospitals to tell families, "Yes, your loved [one] has been admitted to our inpatient unit," or to allow well-negotiated follow-up to prevent relapse, might such legislation lead patients to believe that the content of their discussions with mental health professionals can be relayed to others against their will? Might it serve as one more reason for a troubled individual to avoid care?

From a psychiatrist’s point of view, I might be concerned that I would agree with a patient that information should not be released to family, and nothing about this law would then force me to release it. But would family members feel the law says otherwise? Will they contend, "My family member is mentally ill so HIPAA does not apply, and you must release information to me?" While any given psychiatrist might choose not to release information on any given patient, I wonder if this might be setting us up to be at odds with families, and that would not be a good thing. Much as I’m no fan of HIPAA for many reasons, people do understand the concept that confidentiality is required by law. Perhaps I’m reading too much into this?

Finally, we all agree that eliminating stigma is a good thing when it comes to facilitating voluntary care for those who might need it. But I wonder if we can say that people with mental illnesses are just like everyone else, that this is a medical condition just like other conditions, but for this select group of people they lose their right to privacy, much as children have no right to medical privacy. Might that add to the stigma of mental illness?

I don’t have an answer. I believe the intentions of the Helping Families in Mental Health Crisis Act are good, and I believe they target weaknesses in our system. But I also worry that the legislation might create as many problems as it might fix.

The comments feature of the Clinical Psychiatry News website is turned off for the moment, and I would love to hear your thoughts. Please do e-mail with your comments; I can be reached at [email protected], or you may comment on a similar post here.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

Water droplets

Scientists have discovered an unexpected link between the shape of a cell and its migration efficiency, and they’ve explained its physics using a model of a liquid droplet.

Cell migration is achieved through the movement of the cell’s membrane, which is powered by the action of a protein network inside the cell.

This interaction is affected by the cell’s overall shape, but exactly how this takes place has been unclear.

Research published in Current Biology provides some insight.

The first step in cell migration occurs when the cell extends its front edge—a process called protrusion. This is driven by the growth of actin filaments, which push the cell membrane from inside. At the same time, membrane tension controls protrusion by providing resistance and protecting the cell from over-extending.

But physical laws dictate that the shape of the cell membrane must play a role in the balance between force exerted by actin and the resisting membrane tension. This was not taken into account in previous studies, which used 2D models of migrating cells.

Now, Chiara Gabella, PhD, of Ecole Polytechnique Fédérale de Lausanne in Switzerland, and her colleagues have used a 3D model to better describe the relationship between cell protrusion, shape, and membrane tension.

The scientists developed a way to evaluate the 3D shape of migrating fish epidermal keratocytes by observing the cells in a chamber filled with a fluorescent solution.

The team applied various treatments to swell, shrink, or stretch the cells. And they were able to observe the treatment’s impact on membrane tension, shape, and protrusion velocity.

The treatments only affected the cells’ shape and migration speed, not membrane tension. The results also showed that the more spherical a cell is, the faster it moves.

To interpret these unexpected findings, the scientists modeled a migrating cell as a liquid droplet spreading on a surface.

“It is well known that a droplet’s shape and, in particular, the contact angle that it makes with the surface are determined by the tension forces between the droplet, its environmental medium (eg, air or a different liquid), and the surface on which it moves,” Dr Gabella said.

Results of the modeling experiment suggested that the leading edge could be considered a triple interface between the substrate, membrane, and extracellular medium. And the contact angle between the membrane and the substrate determines the load on actin polymerization and, therefore, the protrusion rate.

“From this point of view, a more spherical cell means less load for actin filaments to overcome and, therefore, faster actin growth and migration,” said Alexander Verkhovsky, PhD, also of Ecole Polytechnique Fédérale de Lausanne.

In support of this idea, the scientists found the cells were sensitive to the surface characteristics, just as droplets would be, by slowing down or being pinned at ridges.

“The emphasis of many studies has been on discovering and characterizing individual cellular components,” Dr Verkhovsky said. “This is rooted in the common belief that a cell’s behavior is determined by intricate networks of genes and proteins.”

In contrast, this work shows that, despite their molecular complexity, cells can be described as physical objects. The findings point to a new relationship between a cell’s shape and its dynamics and may help us to understand how cell migration is guided by the cell’s 3D environment.

Water droplets

Scientists have discovered an unexpected link between the shape of a cell and its migration efficiency, and they’ve explained its physics using a model of a liquid droplet.

Cell migration is achieved through the movement of the cell’s membrane, which is powered by the action of a protein network inside the cell.

This interaction is affected by the cell’s overall shape, but exactly how this takes place has been unclear.

Research published in Current Biology provides some insight.

The first step in cell migration occurs when the cell extends its front edge—a process called protrusion. This is driven by the growth of actin filaments, which push the cell membrane from inside. At the same time, membrane tension controls protrusion by providing resistance and protecting the cell from over-extending.

But physical laws dictate that the shape of the cell membrane must play a role in the balance between force exerted by actin and the resisting membrane tension. This was not taken into account in previous studies, which used 2D models of migrating cells.

Now, Chiara Gabella, PhD, of Ecole Polytechnique Fédérale de Lausanne in Switzerland, and her colleagues have used a 3D model to better describe the relationship between cell protrusion, shape, and membrane tension.

The scientists developed a way to evaluate the 3D shape of migrating fish epidermal keratocytes by observing the cells in a chamber filled with a fluorescent solution.

The team applied various treatments to swell, shrink, or stretch the cells. And they were able to observe the treatment’s impact on membrane tension, shape, and protrusion velocity.

The treatments only affected the cells’ shape and migration speed, not membrane tension. The results also showed that the more spherical a cell is, the faster it moves.

To interpret these unexpected findings, the scientists modeled a migrating cell as a liquid droplet spreading on a surface.

“It is well known that a droplet’s shape and, in particular, the contact angle that it makes with the surface are determined by the tension forces between the droplet, its environmental medium (eg, air or a different liquid), and the surface on which it moves,” Dr Gabella said.

Results of the modeling experiment suggested that the leading edge could be considered a triple interface between the substrate, membrane, and extracellular medium. And the contact angle between the membrane and the substrate determines the load on actin polymerization and, therefore, the protrusion rate.

“From this point of view, a more spherical cell means less load for actin filaments to overcome and, therefore, faster actin growth and migration,” said Alexander Verkhovsky, PhD, also of Ecole Polytechnique Fédérale de Lausanne.

In support of this idea, the scientists found the cells were sensitive to the surface characteristics, just as droplets would be, by slowing down or being pinned at ridges.

“The emphasis of many studies has been on discovering and characterizing individual cellular components,” Dr Verkhovsky said. “This is rooted in the common belief that a cell’s behavior is determined by intricate networks of genes and proteins.”

In contrast, this work shows that, despite their molecular complexity, cells can be described as physical objects. The findings point to a new relationship between a cell’s shape and its dynamics and may help us to understand how cell migration is guided by the cell’s 3D environment.

Water droplets

Scientists have discovered an unexpected link between the shape of a cell and its migration efficiency, and they’ve explained its physics using a model of a liquid droplet.

Cell migration is achieved through the movement of the cell’s membrane, which is powered by the action of a protein network inside the cell.

This interaction is affected by the cell’s overall shape, but exactly how this takes place has been unclear.

Research published in Current Biology provides some insight.

The first step in cell migration occurs when the cell extends its front edge—a process called protrusion. This is driven by the growth of actin filaments, which push the cell membrane from inside. At the same time, membrane tension controls protrusion by providing resistance and protecting the cell from over-extending.

But physical laws dictate that the shape of the cell membrane must play a role in the balance between force exerted by actin and the resisting membrane tension. This was not taken into account in previous studies, which used 2D models of migrating cells.

Now, Chiara Gabella, PhD, of Ecole Polytechnique Fédérale de Lausanne in Switzerland, and her colleagues have used a 3D model to better describe the relationship between cell protrusion, shape, and membrane tension.

The scientists developed a way to evaluate the 3D shape of migrating fish epidermal keratocytes by observing the cells in a chamber filled with a fluorescent solution.

The team applied various treatments to swell, shrink, or stretch the cells. And they were able to observe the treatment’s impact on membrane tension, shape, and protrusion velocity.

The treatments only affected the cells’ shape and migration speed, not membrane tension. The results also showed that the more spherical a cell is, the faster it moves.

To interpret these unexpected findings, the scientists modeled a migrating cell as a liquid droplet spreading on a surface.

“It is well known that a droplet’s shape and, in particular, the contact angle that it makes with the surface are determined by the tension forces between the droplet, its environmental medium (eg, air or a different liquid), and the surface on which it moves,” Dr Gabella said.

Results of the modeling experiment suggested that the leading edge could be considered a triple interface between the substrate, membrane, and extracellular medium. And the contact angle between the membrane and the substrate determines the load on actin polymerization and, therefore, the protrusion rate.

“From this point of view, a more spherical cell means less load for actin filaments to overcome and, therefore, faster actin growth and migration,” said Alexander Verkhovsky, PhD, also of Ecole Polytechnique Fédérale de Lausanne.

In support of this idea, the scientists found the cells were sensitive to the surface characteristics, just as droplets would be, by slowing down or being pinned at ridges.

“The emphasis of many studies has been on discovering and characterizing individual cellular components,” Dr Verkhovsky said. “This is rooted in the common belief that a cell’s behavior is determined by intricate networks of genes and proteins.”

In contrast, this work shows that, despite their molecular complexity, cells can be described as physical objects. The findings point to a new relationship between a cell’s shape and its dynamics and may help us to understand how cell migration is guided by the cell’s 3D environment.

Drug release in a cancer cell

Credit: PNAS

A 2-drug combination can overcome Mcl-1-dependent treatment resistance in multiple myeloma (MM), preclinical research suggests.

The therapy consists of the Chk1 inhibitor CEP3891 and the MEK1/2 inhibitor PD184352.

Chk1 inhibitors prevent cells from arresting in stages of the cell cycle that facilitate DNA repair. And MEK inhibitors prevent cells from activating proteins that regulate DNA repair, while promoting the accumulation of pro-apoptotic proteins.

Researchers recounted their results with the 2 inhibitors in PLOS ONE.

The team noted that, although several drugs are effective against MM, the cancer cells can often survive treatment by increasing production of Mcl-1. This protein regulates processes that promote cell survival and has been implicated in resistance to bortezomib and other anti-myeloma drugs that were initially effective.

With their experiments, the researchers discovered that CEP3891 and PD184352 can reduce Mcl-1 expression and disrupt its interactions with other proteins to effectively kill MM cells.

“This research builds on our previous studies that showed exposing multiple myeloma and leukemia cells to Chk1 inhibitors activated a protective response through the Ras/MEK/ERK signaling pathway,” said Xin-Yan Pei, MD, PhD, of Virginia Commonwealth University and the Massey Cancer Center in Richmond.

“By combining a Chk1 inhibitor with a MEK inhibitor, we have developed one of only a limited number of strategies shown to circumvent therapeutic resistance caused by high expressions of Mcl-1.”

The team began this research by forcing overexpression of Mcl-1 in human MM cells. This caused the cells to become highly resistant to bortezomib, but it failed to protect them from CEP3891 and PD184352.

Furthermore, CEP3891 and PD184352 completely overcame resistance due to microenvironmental factors associated with increased expression of Mcl-1.

“Not only was the combination therapy effective against multiple myeloma cells, it notably did not harm normal bone marrow cells, raising the possibility of therapeutic selectivity,” said study author Steven Grant, MD, also of Virginia Commonwealth University and the Massey Cancer Center.

“We are hopeful that this research will lead to better therapies for multiple myeloma and help make current therapies more effective by overcoming resistance caused by Mcl-1.”

The researchers have started initial discussions with clinical investigators and drug manufacturers about a clinical trial testing a combination of Chk1 and MEK inhibitors in patients with refractory MM.

Drug release in a cancer cell

Credit: PNAS

A 2-drug combination can overcome Mcl-1-dependent treatment resistance in multiple myeloma (MM), preclinical research suggests.

The therapy consists of the Chk1 inhibitor CEP3891 and the MEK1/2 inhibitor PD184352.

Chk1 inhibitors prevent cells from arresting in stages of the cell cycle that facilitate DNA repair. And MEK inhibitors prevent cells from activating proteins that regulate DNA repair, while promoting the accumulation of pro-apoptotic proteins.

Researchers recounted their results with the 2 inhibitors in PLOS ONE.

The team noted that, although several drugs are effective against MM, the cancer cells can often survive treatment by increasing production of Mcl-1. This protein regulates processes that promote cell survival and has been implicated in resistance to bortezomib and other anti-myeloma drugs that were initially effective.

With their experiments, the researchers discovered that CEP3891 and PD184352 can reduce Mcl-1 expression and disrupt its interactions with other proteins to effectively kill MM cells.

“This research builds on our previous studies that showed exposing multiple myeloma and leukemia cells to Chk1 inhibitors activated a protective response through the Ras/MEK/ERK signaling pathway,” said Xin-Yan Pei, MD, PhD, of Virginia Commonwealth University and the Massey Cancer Center in Richmond.

“By combining a Chk1 inhibitor with a MEK inhibitor, we have developed one of only a limited number of strategies shown to circumvent therapeutic resistance caused by high expressions of Mcl-1.”

The team began this research by forcing overexpression of Mcl-1 in human MM cells. This caused the cells to become highly resistant to bortezomib, but it failed to protect them from CEP3891 and PD184352.

Furthermore, CEP3891 and PD184352 completely overcame resistance due to microenvironmental factors associated with increased expression of Mcl-1.

“Not only was the combination therapy effective against multiple myeloma cells, it notably did not harm normal bone marrow cells, raising the possibility of therapeutic selectivity,” said study author Steven Grant, MD, also of Virginia Commonwealth University and the Massey Cancer Center.

“We are hopeful that this research will lead to better therapies for multiple myeloma and help make current therapies more effective by overcoming resistance caused by Mcl-1.”

The researchers have started initial discussions with clinical investigators and drug manufacturers about a clinical trial testing a combination of Chk1 and MEK inhibitors in patients with refractory MM.

Drug release in a cancer cell

Credit: PNAS

A 2-drug combination can overcome Mcl-1-dependent treatment resistance in multiple myeloma (MM), preclinical research suggests.

The therapy consists of the Chk1 inhibitor CEP3891 and the MEK1/2 inhibitor PD184352.

Chk1 inhibitors prevent cells from arresting in stages of the cell cycle that facilitate DNA repair. And MEK inhibitors prevent cells from activating proteins that regulate DNA repair, while promoting the accumulation of pro-apoptotic proteins.

Researchers recounted their results with the 2 inhibitors in PLOS ONE.

The team noted that, although several drugs are effective against MM, the cancer cells can often survive treatment by increasing production of Mcl-1. This protein regulates processes that promote cell survival and has been implicated in resistance to bortezomib and other anti-myeloma drugs that were initially effective.

With their experiments, the researchers discovered that CEP3891 and PD184352 can reduce Mcl-1 expression and disrupt its interactions with other proteins to effectively kill MM cells.

“This research builds on our previous studies that showed exposing multiple myeloma and leukemia cells to Chk1 inhibitors activated a protective response through the Ras/MEK/ERK signaling pathway,” said Xin-Yan Pei, MD, PhD, of Virginia Commonwealth University and the Massey Cancer Center in Richmond.

“By combining a Chk1 inhibitor with a MEK inhibitor, we have developed one of only a limited number of strategies shown to circumvent therapeutic resistance caused by high expressions of Mcl-1.”

The team began this research by forcing overexpression of Mcl-1 in human MM cells. This caused the cells to become highly resistant to bortezomib, but it failed to protect them from CEP3891 and PD184352.

Furthermore, CEP3891 and PD184352 completely overcame resistance due to microenvironmental factors associated with increased expression of Mcl-1.

“Not only was the combination therapy effective against multiple myeloma cells, it notably did not harm normal bone marrow cells, raising the possibility of therapeutic selectivity,” said study author Steven Grant, MD, also of Virginia Commonwealth University and the Massey Cancer Center.

“We are hopeful that this research will lead to better therapies for multiple myeloma and help make current therapies more effective by overcoming resistance caused by Mcl-1.”

The researchers have started initial discussions with clinical investigators and drug manufacturers about a clinical trial testing a combination of Chk1 and MEK inhibitors in patients with refractory MM.