Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Americans who live in rural areas are more likely than their urban counterparts are to die of the 5 leading causes of death, according to a CDC study of data from the National Vital Statistics System.

In 2014, 25,000 rural residents died of heart disease, 19,000 of cancer, 12,000 of unintentional injuries, 11,000 of chronic lower respiratory disease, and 4,000 of stroke. The study also found that unintentional injury deaths were about 50% higher in rural areas than in urban areas, partly due to a greater risk of death in vehicle crashes and of opioid overdoses. The problem is compounded by the fact that the distance between health care facilities and trauma centers can make rapid access to specialized health care difficult.

The study researchers say several factors could influence the rural-urban gap. For instance, many of the deaths are associated with sociodemographic differences. Rural residents tend to be older, poorer, and sicker with limited physical activity due to chronic conditions. But that “striking gap” in health can be closed, says CDC Director Tom Frieden, MD, MPH, by better understanding and addressing the health threats that put rural Americans at risk.

CDC suggests, for instance, that health care providers in rural areas:

• Screen patients for high blood pressure and make control a quality improvement goal;
• Increase cancer prevention and early detection—for example, by participating in state-level comprehensive control coalitions, which focus on prevention, education, screening, access, support, and overall good health;
• Encourage physical activity and healthy eating to reduce obesity;
• Encourage patients to stop smoking;
• Promote vehicle safety (rural residents are less likely to use seatbelts); and
• Engage in safe prescribing of opioids for pain, and use nonpharmacologic therapies

The report and a companion commentary are part of a new rural health series in CDC’s Morbidity and Mortality Weekly Report. The Health Resources and Services Administration, which houses the Federal Office of Rural Health Policy, will collaborate with the CDC on the series and help promote the findings and recommendations to rural communities.

Americans who live in rural areas are more likely than their urban counterparts are to die of the 5 leading causes of death, according to a CDC study of data from the National Vital Statistics System.

In 2014, 25,000 rural residents died of heart disease, 19,000 of cancer, 12,000 of unintentional injuries, 11,000 of chronic lower respiratory disease, and 4,000 of stroke. The study also found that unintentional injury deaths were about 50% higher in rural areas than in urban areas, partly due to a greater risk of death in vehicle crashes and of opioid overdoses. The problem is compounded by the fact that the distance between health care facilities and trauma centers can make rapid access to specialized health care difficult.

The study researchers say several factors could influence the rural-urban gap. For instance, many of the deaths are associated with sociodemographic differences. Rural residents tend to be older, poorer, and sicker with limited physical activity due to chronic conditions. But that “striking gap” in health can be closed, says CDC Director Tom Frieden, MD, MPH, by better understanding and addressing the health threats that put rural Americans at risk.

CDC suggests, for instance, that health care providers in rural areas:

• Screen patients for high blood pressure and make control a quality improvement goal;
• Increase cancer prevention and early detection—for example, by participating in state-level comprehensive control coalitions, which focus on prevention, education, screening, access, support, and overall good health;
• Encourage physical activity and healthy eating to reduce obesity;
• Encourage patients to stop smoking;
• Promote vehicle safety (rural residents are less likely to use seatbelts); and
• Engage in safe prescribing of opioids for pain, and use nonpharmacologic therapies

The report and a companion commentary are part of a new rural health series in CDC’s Morbidity and Mortality Weekly Report. The Health Resources and Services Administration, which houses the Federal Office of Rural Health Policy, will collaborate with the CDC on the series and help promote the findings and recommendations to rural communities.

Americans who live in rural areas are more likely than their urban counterparts are to die of the 5 leading causes of death, according to a CDC study of data from the National Vital Statistics System.

In 2014, 25,000 rural residents died of heart disease, 19,000 of cancer, 12,000 of unintentional injuries, 11,000 of chronic lower respiratory disease, and 4,000 of stroke. The study also found that unintentional injury deaths were about 50% higher in rural areas than in urban areas, partly due to a greater risk of death in vehicle crashes and of opioid overdoses. The problem is compounded by the fact that the distance between health care facilities and trauma centers can make rapid access to specialized health care difficult.

The study researchers say several factors could influence the rural-urban gap. For instance, many of the deaths are associated with sociodemographic differences. Rural residents tend to be older, poorer, and sicker with limited physical activity due to chronic conditions. But that “striking gap” in health can be closed, says CDC Director Tom Frieden, MD, MPH, by better understanding and addressing the health threats that put rural Americans at risk.

CDC suggests, for instance, that health care providers in rural areas:

• Screen patients for high blood pressure and make control a quality improvement goal;
• Increase cancer prevention and early detection—for example, by participating in state-level comprehensive control coalitions, which focus on prevention, education, screening, access, support, and overall good health;
• Encourage physical activity and healthy eating to reduce obesity;
• Encourage patients to stop smoking;
• Promote vehicle safety (rural residents are less likely to use seatbelts); and
• Engage in safe prescribing of opioids for pain, and use nonpharmacologic therapies

The report and a companion commentary are part of a new rural health series in CDC’s Morbidity and Mortality Weekly Report. The Health Resources and Services Administration, which houses the Federal Office of Rural Health Policy, will collaborate with the CDC on the series and help promote the findings and recommendations to rural communities.

Daptomycin was safe and effective at treating complicated skin and skin structure infections (cSSSI) in children aged 1-17 years, according to Dr. John Bradley of the University of California, San Diego, and his associates.

A total of 389 cSSSI patients were included in the study, with 257 receiving daptomycin and 132 receiving standard-of-care (SOC) treatment (mostly vancomycin or clindamycin). Clinical success rates were similar for both groups, at 91% in the daptomycin group and 87% in the SOC group. Therapeutic success rates also were similar, at 97% in the daptomycin group and 99% in the SOC group.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Daptomycin was safe and effective at treating complicated skin and skin structure infections (cSSSI) in children aged 1-17 years, according to Dr. John Bradley of the University of California, San Diego, and his associates.

A total of 389 cSSSI patients were included in the study, with 257 receiving daptomycin and 132 receiving standard-of-care (SOC) treatment (mostly vancomycin or clindamycin). Clinical success rates were similar for both groups, at 91% in the daptomycin group and 87% in the SOC group. Therapeutic success rates also were similar, at 97% in the daptomycin group and 99% in the SOC group.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Daptomycin was safe and effective at treating complicated skin and skin structure infections (cSSSI) in children aged 1-17 years, according to Dr. John Bradley of the University of California, San Diego, and his associates.

A total of 389 cSSSI patients were included in the study, with 257 receiving daptomycin and 132 receiving standard-of-care (SOC) treatment (mostly vancomycin or clindamycin). Clinical success rates were similar for both groups, at 91% in the daptomycin group and 87% in the SOC group. Therapeutic success rates also were similar, at 97% in the daptomycin group and 99% in the SOC group.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Clinical question: Does proactive home- and clinic-based palliative care impact hospital use and health care cost in Medicare Advantage beneficiaries?

Background: Studies demonstrate that community-based palliative care is becoming more common because of the need to better deliver individualized care, the positive effects on patient experience and outcomes, and payment model changes exerting pressure to reduce hospital use and cost.

Study design: Observational, retrospective study using propensity-based matching.

Setting: Southern California Health System.

Synopsis: Using the health systems’ databases of 368 community-based palliative care participants compared with 1,075 matched, non–palliative care individuals, this study showed that community-based palliative care participants had less hospital use and lower hospital costs than did the non–palliative care participants, which drove lower overall health care costs.

Hospitalists managing patients with acute exacerbations of chronic diseases and cancer should consider referral to ambulatory palliative care or comprehensive transitional care programs.

Bottom line: Proactive, ambulatory patient-centered palliative care lowers hospitalizations and end-of-life care costs.

Citations: Cassel JB, Kerr KM, McClish DK, et al. Effect of a Home-Based Palliative Care Program on Healthcare Use and Costs. J Am Geriatr Soc. 64:2288-2295, 2016.
 

Dr. McAllister is a hospitalist, assistant professor of medicine, and medical director of transitional care in the Department of Hospital Medicine at Cooper University Hospital, Camden, N.J.

Clinical question: Does proactive home- and clinic-based palliative care impact hospital use and health care cost in Medicare Advantage beneficiaries?

Background: Studies demonstrate that community-based palliative care is becoming more common because of the need to better deliver individualized care, the positive effects on patient experience and outcomes, and payment model changes exerting pressure to reduce hospital use and cost.

Study design: Observational, retrospective study using propensity-based matching.

Setting: Southern California Health System.

Synopsis: Using the health systems’ databases of 368 community-based palliative care participants compared with 1,075 matched, non–palliative care individuals, this study showed that community-based palliative care participants had less hospital use and lower hospital costs than did the non–palliative care participants, which drove lower overall health care costs.

Hospitalists managing patients with acute exacerbations of chronic diseases and cancer should consider referral to ambulatory palliative care or comprehensive transitional care programs.

Bottom line: Proactive, ambulatory patient-centered palliative care lowers hospitalizations and end-of-life care costs.

Citations: Cassel JB, Kerr KM, McClish DK, et al. Effect of a Home-Based Palliative Care Program on Healthcare Use and Costs. J Am Geriatr Soc. 64:2288-2295, 2016.
 

Dr. McAllister is a hospitalist, assistant professor of medicine, and medical director of transitional care in the Department of Hospital Medicine at Cooper University Hospital, Camden, N.J.

Clinical question: Does proactive home- and clinic-based palliative care impact hospital use and health care cost in Medicare Advantage beneficiaries?

Background: Studies demonstrate that community-based palliative care is becoming more common because of the need to better deliver individualized care, the positive effects on patient experience and outcomes, and payment model changes exerting pressure to reduce hospital use and cost.

Study design: Observational, retrospective study using propensity-based matching.

Setting: Southern California Health System.

Synopsis: Using the health systems’ databases of 368 community-based palliative care participants compared with 1,075 matched, non–palliative care individuals, this study showed that community-based palliative care participants had less hospital use and lower hospital costs than did the non–palliative care participants, which drove lower overall health care costs.

Hospitalists managing patients with acute exacerbations of chronic diseases and cancer should consider referral to ambulatory palliative care or comprehensive transitional care programs.

Bottom line: Proactive, ambulatory patient-centered palliative care lowers hospitalizations and end-of-life care costs.

Citations: Cassel JB, Kerr KM, McClish DK, et al. Effect of a Home-Based Palliative Care Program on Healthcare Use and Costs. J Am Geriatr Soc. 64:2288-2295, 2016.
 

Dr. McAllister is a hospitalist, assistant professor of medicine, and medical director of transitional care in the Department of Hospital Medicine at Cooper University Hospital, Camden, N.J.

I have a breakthrough article to share with you. It’s about a technology that detects skin cancer. Before I tell you about that, however, I need to teach you a few things. For example, do you know what AI is? How about machine learning? What about CNN? (This column is a nonpolitical arena, so, no, not that CNN).

AI stands for artificial intelligence. We are surrounded by it everywhere – computers, cars, and cell phones all use AI. AI describes a machine with the ability to problem solve, to create, to understand, to learn. These are characteristics we call “intelligence,” hence, artificial intelligence.

Dr. Benabio is a partner physician and chief of service for the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected] . He has no disclosures related to this column.

I have a breakthrough article to share with you. It’s about a technology that detects skin cancer. Before I tell you about that, however, I need to teach you a few things. For example, do you know what AI is? How about machine learning? What about CNN? (This column is a nonpolitical arena, so, no, not that CNN).

AI stands for artificial intelligence. We are surrounded by it everywhere – computers, cars, and cell phones all use AI. AI describes a machine with the ability to problem solve, to create, to understand, to learn. These are characteristics we call “intelligence,” hence, artificial intelligence.

Dr. Benabio is a partner physician and chief of service for the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected] . He has no disclosures related to this column.

I have a breakthrough article to share with you. It’s about a technology that detects skin cancer. Before I tell you about that, however, I need to teach you a few things. For example, do you know what AI is? How about machine learning? What about CNN? (This column is a nonpolitical arena, so, no, not that CNN).

AI stands for artificial intelligence. We are surrounded by it everywhere – computers, cars, and cell phones all use AI. AI describes a machine with the ability to problem solve, to create, to understand, to learn. These are characteristics we call “intelligence,” hence, artificial intelligence.

Dr. Benabio is a partner physician and chief of service for the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected] . He has no disclosures related to this column.

Rates of herpes zoster infections have increased substantially since the late 1990s in Canada. This, combined with rising per-episode medical costs and constant per-episode drug costs has led to increased total outpatient costs. But this has been offset by a dramatic drop in hospitalization rates and costs, according to a study published by BMC Infectious Diseases.

“A number of recent studies have looked at the burden of HZ-PHN [herpes zoster–postherpetic neuralgia] in a variety of health care systems, including Belgium, France, Germany, Greece, Italy, Spain, the United Kingdom, and Israel. However, little recent Canadian data have been published,” wrote Kevin J. Friesen, MD, and his associates at the University of Manitoba, Winnipeg, explaining that the goal of this study was to “establish the current burden of HZ and PHN in the setting of a universal health care system, and to look at long-term trends in their treatment costs.”

©Elsevier 2004. Habif: Clinical Dermatology 4E

[email protected]

Rates of herpes zoster infections have increased substantially since the late 1990s in Canada. This, combined with rising per-episode medical costs and constant per-episode drug costs has led to increased total outpatient costs. But this has been offset by a dramatic drop in hospitalization rates and costs, according to a study published by BMC Infectious Diseases.

“A number of recent studies have looked at the burden of HZ-PHN [herpes zoster–postherpetic neuralgia] in a variety of health care systems, including Belgium, France, Germany, Greece, Italy, Spain, the United Kingdom, and Israel. However, little recent Canadian data have been published,” wrote Kevin J. Friesen, MD, and his associates at the University of Manitoba, Winnipeg, explaining that the goal of this study was to “establish the current burden of HZ and PHN in the setting of a universal health care system, and to look at long-term trends in their treatment costs.”

©Elsevier 2004. Habif: Clinical Dermatology 4E

[email protected]

Rates of herpes zoster infections have increased substantially since the late 1990s in Canada. This, combined with rising per-episode medical costs and constant per-episode drug costs has led to increased total outpatient costs. But this has been offset by a dramatic drop in hospitalization rates and costs, according to a study published by BMC Infectious Diseases.

“A number of recent studies have looked at the burden of HZ-PHN [herpes zoster–postherpetic neuralgia] in a variety of health care systems, including Belgium, France, Germany, Greece, Italy, Spain, the United Kingdom, and Israel. However, little recent Canadian data have been published,” wrote Kevin J. Friesen, MD, and his associates at the University of Manitoba, Winnipeg, explaining that the goal of this study was to “establish the current burden of HZ and PHN in the setting of a universal health care system, and to look at long-term trends in their treatment costs.”

©Elsevier 2004. Habif: Clinical Dermatology 4E

[email protected]

WASHINGTON – The Medicare Payment Advisory Commission is putting the finishing touches on a recommendation for a hybrid approach to reforming how Medicare pays doctors for drugs administered in the office.

If adopted by the Centers for Medicare & Medicaid Services, MedPAC’s recommendations first would refine the current system which pays physicians for Medicare Part B drugs based on the average sales price (ASP), then eventually would allow physicians to either remain in the improved ASP system or switch to a drug value program (DVP), a revamped version of the failed Competitive Acquisition Program.

anttohoho/Thinkstock

[email protected]
 

WASHINGTON – The Medicare Payment Advisory Commission is putting the finishing touches on a recommendation for a hybrid approach to reforming how Medicare pays doctors for drugs administered in the office.

If adopted by the Centers for Medicare & Medicaid Services, MedPAC’s recommendations first would refine the current system which pays physicians for Medicare Part B drugs based on the average sales price (ASP), then eventually would allow physicians to either remain in the improved ASP system or switch to a drug value program (DVP), a revamped version of the failed Competitive Acquisition Program.

anttohoho/Thinkstock

[email protected]
 

WASHINGTON – The Medicare Payment Advisory Commission is putting the finishing touches on a recommendation for a hybrid approach to reforming how Medicare pays doctors for drugs administered in the office.

If adopted by the Centers for Medicare & Medicaid Services, MedPAC’s recommendations first would refine the current system which pays physicians for Medicare Part B drugs based on the average sales price (ASP), then eventually would allow physicians to either remain in the improved ASP system or switch to a drug value program (DVP), a revamped version of the failed Competitive Acquisition Program.

anttohoho/Thinkstock

[email protected]
 

Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.

Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.

“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.

Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).

“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.

Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”

“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”

Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.

“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.

Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.

Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.

“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.

Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).

“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.

Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”

“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”

Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.

“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.

Antibiotics may hamper the effectiveness of immune checkpoint inhibitors for patients with metastatic renal cell carcinoma, according to a small, retrospective study. Using antibiotics within 1 month of starting a checkpoint inhibitor was associated with significantly shorter progression-free survival, as well as a trend toward shorter overall survival, in a study of 80 patients with metastatic renal cell carcinoma.

Although the mechanism remains unknown, the prevailing theory is that antibiotics adversely alter the composition of the gut microbiome, and in so doing, slash the ability of beneficial bacteria to boost efficacy of immune checkpoint blockade.

“The data I presented today are just preliminary. But the results are really important because there is a kind of connection between the microbiome, antibiotics, and immune checkpoint blockade,” Lisa Derosa, MD, of Paris-Sud University, Villejuif, France, said during a press briefing prior to the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Derosa and her colleagues retrospectively assessed 80 people with metastatic renal cell carcinoma enrolled in prospective trials at Gustave Roussy Cancer Institute. The patients were treated with the PD1/PD-L1 inhibitors alone or in combination. The researchers compared survival of 16 patients who also received broad-spectrum antibiotic therapy within 1 month of their first dose of immunotherapy with 64 others who did not receive antibiotics.

Progression-free survival was significantly shorter for patients in the antibiotic group, 2.3 months versus 8.1 months for the nonantibiotic group (P less than .001) on Kaplan-Meier curves. The statistical significance persisted even after the researchers controlled for age, gender, International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumor burden, and PPI use in a multivariate analysis. Similarly, the objective response rate to checkpoint inhibition therapy was significantly lower among patients in the antibiotic group (P less than .002).

“There was no significant difference, however, between these groups in overall survival,” Dr. Derosa said.

Despite the findings, Dr. Derosa said it’s too soon to say antibiotics are contraindicated in this patient population. “It may be important to pay attention to these antibiotics in patients treated with immune response inhibitors, but the data are still preliminary.”

“I would propose this data is very intriguing, but it was retrospectively generated, so I consider it hypothesis-generating,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif., and moderator of the press briefing. “One has to consider the fact that antibiotics are used under circumstances of medical necessity. I wouldn’t forgo treatment of any active infection … I would use as medically necessary.”

Beta-lactamases and fluoroquinolones comprised the majority of antibiotics in the study. The majority, 67 patients, received immune monotherapy with single-agent PD-1 or PD-L1 inhibitors. Another 10 patients received a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, and 3 were treated with a PD-L1 inhibitor and bevacizumab.

“This is the first analysis evaluating impact of antibiotics on outcome of advanced renal carcinoma patients treated in the era of immune checkpoint blockade,” Dr. Derosa said. “We have a lot of work to do.” She and her colleagues plan to continue enrolling patients in the study. They also plan to evaluate whether alteration of the microbiome composition does play a role in diminishing the effectiveness of immunotherapy, and if so, which types of bacteria are the most likely culprits.