Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

[email protected]

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

[email protected]

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

[email protected]

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

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Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

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Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

[email protected]

On Twitter @jessnicolecraig

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

[email protected]

On Twitter @jessnicolecraig

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

[email protected]

On Twitter @jessnicolecraig

NEW ORLEANS – When Mayo Clinic physicians noticed some patients on appropriate antibiotic treatment for Staphylococcus aureus bacteremia cleared the infection, only to see it recur a few days later, Justin A. Fiala, MD and his colleagues grew curious.

Dr. Fiala, an infectious diseases internist at Mayo Clinic, Rochester, Minn., was intrigued by the possibility of fluctuating blood culture positivity in this subset of bacteremia patients.

“We wanted first to see whether or not this is a real entity and determine the prevalence of this ‘skip pattern,’” Dr. Fiala said at IDWeek 2016, the annual combined meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association and the Pediatric Infectious Diseases Society. He said identifying predictors and finding any differences in clinical outcomes compared to control S. aureus bacteremia (SAB) patients were additional aims.

Dr. Fiala and his colleagues assessed a hospitalized cohort of 726 adults with SAB at Mayo Clinic between July 2006 and June 2011. Patients with one or more negative blood cultures followed by a positive culture were identified within this group, and compared with 2 to 4 patients matched for age, sex and duration of bacteremia who served as controls.

The investigators found 29 patients – or 4% – of the 726 had this ‘skip pattern’ of infection, clearance, and reinfection. Those with the phenomenon were 90% male and tended to be older, with a mean age of 69 years, compared to the controls. They had index bacteremia about two days longer than controls. The study also revealed a significant difference in mean number of central venous catheters: 2.7 in the skip phenomenon group versus 1.7 in controls.

©CDC/Janice Haney Carr

NEW ORLEANS – When Mayo Clinic physicians noticed some patients on appropriate antibiotic treatment for Staphylococcus aureus bacteremia cleared the infection, only to see it recur a few days later, Justin A. Fiala, MD and his colleagues grew curious.

Dr. Fiala, an infectious diseases internist at Mayo Clinic, Rochester, Minn., was intrigued by the possibility of fluctuating blood culture positivity in this subset of bacteremia patients.

“We wanted first to see whether or not this is a real entity and determine the prevalence of this ‘skip pattern,’” Dr. Fiala said at IDWeek 2016, the annual combined meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association and the Pediatric Infectious Diseases Society. He said identifying predictors and finding any differences in clinical outcomes compared to control S. aureus bacteremia (SAB) patients were additional aims.

Dr. Fiala and his colleagues assessed a hospitalized cohort of 726 adults with SAB at Mayo Clinic between July 2006 and June 2011. Patients with one or more negative blood cultures followed by a positive culture were identified within this group, and compared with 2 to 4 patients matched for age, sex and duration of bacteremia who served as controls.

The investigators found 29 patients – or 4% – of the 726 had this ‘skip pattern’ of infection, clearance, and reinfection. Those with the phenomenon were 90% male and tended to be older, with a mean age of 69 years, compared to the controls. They had index bacteremia about two days longer than controls. The study also revealed a significant difference in mean number of central venous catheters: 2.7 in the skip phenomenon group versus 1.7 in controls.

©CDC/Janice Haney Carr

NEW ORLEANS – When Mayo Clinic physicians noticed some patients on appropriate antibiotic treatment for Staphylococcus aureus bacteremia cleared the infection, only to see it recur a few days later, Justin A. Fiala, MD and his colleagues grew curious.

Dr. Fiala, an infectious diseases internist at Mayo Clinic, Rochester, Minn., was intrigued by the possibility of fluctuating blood culture positivity in this subset of bacteremia patients.

“We wanted first to see whether or not this is a real entity and determine the prevalence of this ‘skip pattern,’” Dr. Fiala said at IDWeek 2016, the annual combined meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association and the Pediatric Infectious Diseases Society. He said identifying predictors and finding any differences in clinical outcomes compared to control S. aureus bacteremia (SAB) patients were additional aims.

Dr. Fiala and his colleagues assessed a hospitalized cohort of 726 adults with SAB at Mayo Clinic between July 2006 and June 2011. Patients with one or more negative blood cultures followed by a positive culture were identified within this group, and compared with 2 to 4 patients matched for age, sex and duration of bacteremia who served as controls.

The investigators found 29 patients – or 4% – of the 726 had this ‘skip pattern’ of infection, clearance, and reinfection. Those with the phenomenon were 90% male and tended to be older, with a mean age of 69 years, compared to the controls. They had index bacteremia about two days longer than controls. The study also revealed a significant difference in mean number of central venous catheters: 2.7 in the skip phenomenon group versus 1.7 in controls.

©CDC/Janice Haney Carr

ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.

Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.

Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.

Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

A recent neurocognitive study found that executive dysfunction persists among young adults with perinatal HIV infection in comparison to controls.

Interventions designed for the prevention of mother-to-child transmission of HIV infection have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

HIV pre-exposure prophylaxis (PrEP) use reduced fear and shame associated with sex and facilitated greater sexual satisfaction and intimacy among men who have sex with men, according to a study by investigators at the University of Washington.

A study in HIV Medicine found that several of the World Health Organization’s HIV drug resistance (HIVDR) early warning indicators (EWIs) were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available.

Findings from a large multi-center Ethiopian study suggest that sub-optimal adherence to combination antiretroviral therapy (cART) was present in up to a quarter of HIV patients, despite a high degree of average adherence to cART.

Developing strategies and interventions to facilitate parent–adolescent communication about sex-related topics, particularly HIV prevention and condom use, may be important to increase HIV testing among young women and men, according to a study in AIDS Care.

A French study found that comorbidities and coprescriptions are highly prevalent in ageing HIV-infected patients, especially those with a long history of HIV infection.

A review article in AIDS Research and Therapy noted that HIV-associated pulmonary tuberculosis treatment mandates a committed approach that encompasses both effective as well as enduring therapy originating from newer drug combinations, evolving ideas and emerging concepts from clinical trials globally.

Home-based HIV testing remains an efficient strategy to diagnose and link to care in settings with high levels of HIV awareness, according to a recent study in Chiradzulu District, Malawi.

A recent study suggests that obesity is an additional health burden to people living with HIV and that their daily dietary practices are not meeting the U.S. government-recommended nutritional standards.

Implementation of the Affordable Care Act was followed by HIV-positive patient enrollment growth and improved viral control in Kaiser Permanente Northern California, according to a study in JAIDS.

A pediatric study found that the statin drug atorvastatin lowered total cholesterol, LDL cholesterol, non-HDL cholesterol and apolipoprotein B in HIV-infected youth with antiretroviral-associated hyperlipidemia. The authors said atorvastatin could be considered for HIV-infected children with hyperlipidemia.

Subsequent to the initiation of combination antiretroviral therapy (cART) in HIV patients, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function.

Among malnourished antiretroviral-eligible HIV-positive adults in Zambia and Tanzania, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events.

A study in JAIDS found that drug regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide plus darunavir has durable maintenance of virologic suppression and improvements in specific markers of renal safety.

An analysis in BMC Infectious Diseases revealed that the clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary antiretroviral drugs.

Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anemia on prescription of antiretroviral therapy could likely improve the health conditions of HIV-infected children.
 

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

A recent neurocognitive study found that executive dysfunction persists among young adults with perinatal HIV infection in comparison to controls.

Interventions designed for the prevention of mother-to-child transmission of HIV infection have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

HIV pre-exposure prophylaxis (PrEP) use reduced fear and shame associated with sex and facilitated greater sexual satisfaction and intimacy among men who have sex with men, according to a study by investigators at the University of Washington.

A study in HIV Medicine found that several of the World Health Organization’s HIV drug resistance (HIVDR) early warning indicators (EWIs) were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available.

Findings from a large multi-center Ethiopian study suggest that sub-optimal adherence to combination antiretroviral therapy (cART) was present in up to a quarter of HIV patients, despite a high degree of average adherence to cART.

Developing strategies and interventions to facilitate parent–adolescent communication about sex-related topics, particularly HIV prevention and condom use, may be important to increase HIV testing among young women and men, according to a study in AIDS Care.

A French study found that comorbidities and coprescriptions are highly prevalent in ageing HIV-infected patients, especially those with a long history of HIV infection.

A review article in AIDS Research and Therapy noted that HIV-associated pulmonary tuberculosis treatment mandates a committed approach that encompasses both effective as well as enduring therapy originating from newer drug combinations, evolving ideas and emerging concepts from clinical trials globally.

Home-based HIV testing remains an efficient strategy to diagnose and link to care in settings with high levels of HIV awareness, according to a recent study in Chiradzulu District, Malawi.

A recent study suggests that obesity is an additional health burden to people living with HIV and that their daily dietary practices are not meeting the U.S. government-recommended nutritional standards.

Implementation of the Affordable Care Act was followed by HIV-positive patient enrollment growth and improved viral control in Kaiser Permanente Northern California, according to a study in JAIDS.

A pediatric study found that the statin drug atorvastatin lowered total cholesterol, LDL cholesterol, non-HDL cholesterol and apolipoprotein B in HIV-infected youth with antiretroviral-associated hyperlipidemia. The authors said atorvastatin could be considered for HIV-infected children with hyperlipidemia.

Subsequent to the initiation of combination antiretroviral therapy (cART) in HIV patients, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function.

Among malnourished antiretroviral-eligible HIV-positive adults in Zambia and Tanzania, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events.

A study in JAIDS found that drug regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide plus darunavir has durable maintenance of virologic suppression and improvements in specific markers of renal safety.

An analysis in BMC Infectious Diseases revealed that the clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary antiretroviral drugs.

Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anemia on prescription of antiretroviral therapy could likely improve the health conditions of HIV-infected children.
 

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

A recent neurocognitive study found that executive dysfunction persists among young adults with perinatal HIV infection in comparison to controls.

Interventions designed for the prevention of mother-to-child transmission of HIV infection have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

HIV pre-exposure prophylaxis (PrEP) use reduced fear and shame associated with sex and facilitated greater sexual satisfaction and intimacy among men who have sex with men, according to a study by investigators at the University of Washington.

A study in HIV Medicine found that several of the World Health Organization’s HIV drug resistance (HIVDR) early warning indicators (EWIs) were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available.

Findings from a large multi-center Ethiopian study suggest that sub-optimal adherence to combination antiretroviral therapy (cART) was present in up to a quarter of HIV patients, despite a high degree of average adherence to cART.

Developing strategies and interventions to facilitate parent–adolescent communication about sex-related topics, particularly HIV prevention and condom use, may be important to increase HIV testing among young women and men, according to a study in AIDS Care.

A French study found that comorbidities and coprescriptions are highly prevalent in ageing HIV-infected patients, especially those with a long history of HIV infection.

A review article in AIDS Research and Therapy noted that HIV-associated pulmonary tuberculosis treatment mandates a committed approach that encompasses both effective as well as enduring therapy originating from newer drug combinations, evolving ideas and emerging concepts from clinical trials globally.

Home-based HIV testing remains an efficient strategy to diagnose and link to care in settings with high levels of HIV awareness, according to a recent study in Chiradzulu District, Malawi.

A recent study suggests that obesity is an additional health burden to people living with HIV and that their daily dietary practices are not meeting the U.S. government-recommended nutritional standards.

Implementation of the Affordable Care Act was followed by HIV-positive patient enrollment growth and improved viral control in Kaiser Permanente Northern California, according to a study in JAIDS.

A pediatric study found that the statin drug atorvastatin lowered total cholesterol, LDL cholesterol, non-HDL cholesterol and apolipoprotein B in HIV-infected youth with antiretroviral-associated hyperlipidemia. The authors said atorvastatin could be considered for HIV-infected children with hyperlipidemia.

Subsequent to the initiation of combination antiretroviral therapy (cART) in HIV patients, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function.

Among malnourished antiretroviral-eligible HIV-positive adults in Zambia and Tanzania, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events.

A study in JAIDS found that drug regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide plus darunavir has durable maintenance of virologic suppression and improvements in specific markers of renal safety.

An analysis in BMC Infectious Diseases revealed that the clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary antiretroviral drugs.

Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anemia on prescription of antiretroviral therapy could likely improve the health conditions of HIV-infected children.
 

[email protected]

On Twitter @richpizzi

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.