Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Blood samples

Credit: Graham Colm

Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).

The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.

The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.

“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “By the time the X-rays show something, the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”

To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.

As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine: different isotopes of a chemical element can react at slightly different rates.

An earlier study testing this technique in healthy subjects showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.

In healthy, active humans, bone is forming at about the same rate as it resorbs. But if bone loss is occurring, the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured using precise mass spectrometry methods.

Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.

The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ^44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.

For MM patients specifically, those with active disease had a significantly lower mean δ^44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter ⁴²Ca.

Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.

“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”

Child with leukemia

Credit: Bill Branson

Childhood cancer survivors are no more likely than their cancer-free peers to adhere to healthy living guidelines, according to a study published in the Journal of Cancer Survivorship.

Survivors were less likely to be smokers and had a lower average body mass index (BMI).

But there were no significant differences between survivors and cancer-free control subjects with regard to overall diet, physical activity, or alcohol consumption.

Chloe Berdan, of Promedica in Toledo, Ohio, and her colleagues uncovered these results by examining data from the Chicago Healthy Living Study.

The team assessed adherence to American Cancer Society Guidelines on Nutrition and Physical Activity via interviews with 431 childhood cancer survivors and 361 control subjects who never had cancer. The survivors, ages 18 to 59, were all diagnosed with a malignant cancer before their 21st birthdays.

There were no significant differences in sex or race between survivors and controls. Survivors were younger than controls (28.4±7.8 vs 29.6± 8.3 years, P=0.04) and had less education (14.0±2.0 vs 14.4±2.0 years, P=0.01).

Overall, there was no significant difference between survivors and control subjects in adhering to the American Cancer Society guidelines.

Survivors and controls also had similar scores for several individual measures, including alcohol consumption, overall physical activity, overall diet, the servings of fruits/vegetables consumed, and the consumption of red/processed meat.

However, survivors were significantly less likely than controls to be smokers—11.4% vs 17.5% (P=0.02). Survivors had, on average, a BMI of about 1.2 kg/m² lower than controls (P=0.01). And survivors consumed significantly less fiber than controls—9.2±3.5 vs 9.7±3.8 kcal (P=0.05).

Only about 1 in 10 survivors (10.2%) met fiber recommendations, 17.7% ate 5 fruits or vegetables per day, and 46.2% met the red/processed meat recommendation of less than 18 oz per week. On average, survivors scored under 50% for the quality of their diets.

Survivors were better at meeting the goal of at least 5 hours of moderate activity per week (60.5%) than to sticking to any of the other guidelines.

About 36% of survivors were within a healthy BMI range, 2.9% were underweight, 28.9% were overweight, and 32.4% were obese.

The 0.7% of survivors who adhered fully to the guidelines tended to be women, non-smokers, and people with a good view of their own health.

“There is still much room for improvement in educating and encouraging survivors to follow healthier diets and lifestyles,” Berdan said. “Adopting such behavior during early adulthood may have a lasting impact on their quality of life and overall survival.”

Study authors Jacquin Niles

(left) and Jeffrey Wagner

Credit: Bryce Vickmark

The gene-editing technique CRISPR can disrupt a single gene from the malaria parasite Plasmodium falciparum in a matter of weeks, a new study suggests.

Although CRISPR’s success rate ranged from 50% to 100%, the researchers believe the technique shows promise and could greatly speed up gene analysis.

At present, it can take up to a year to determine the function of a single gene in P falciparum, which can hinder efforts to develop drugs and vaccines.

“Even though we’ve sequenced the entire genome of Plasmodium falciparum, half of it still remains functionally uncharacterized,” said Jacquin Niles, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.

“That’s about 2500 genes that, if only we knew what they did, we could think about novel therapeutics, whether it’s drugs or vaccines.”

Dr Niles and his colleagues described their use of CRISPR in P falciparum in Nature Methods.

The team noted that, in P falciparum, gene editing can take up to a year because it relies on homologous recombination, a type of genetic swapping that cells use to repair broken DNA strands and that occurs very rarely in the genome of the malaria parasite.

“You have to rely on this really inefficient process that occurs only if you have spontaneous DNA strand breaks that happen to fall within your region of interest,” Dr Niles said.

More recently, researchers have successfully used zinc finger nucleases to cut out specific genes, but this approach is costly because it requires a new nuclease to be designed for each gene target.

CRISPR exploits a set of bacterial proteins that protect microbes from viral infection. The system includes a DNA-cutting enzyme, Cas9, bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. This approach allows scientists to target and delete any gene by simply changing the RNA guide strand sequence.

As soon as researchers proved this system could work in cells other than bacteria, Dr Niles started to think about using it to manipulate P falciparum.

To test this approach, he and his colleagues tried using CRISPR to disrupt 2 genes, kahrp and eba-175, that had previously been knocked out in malaria using traditional approaches.

The kahrp gene produces a protein that causes red blood cells to develop a knobby appearance when infected with malaria. Dr Niles’s team was able to disrupt this gene in 100% of parasites treated with the CRISPR system. The red blood cells infected by parasites remained smooth.

The other gene, eba-175, codes for a protein that binds to red blood cell receptors and helps the malaria parasite enter cells. The researchers were only able to disrupt this gene in 50% to 80% of parasites manipulated with CRISPR.

“We consider this to be a win,” Dr Niles said. “Compared to the efficiency with which P falciparum genetics have been done in the past, even 50% is pretty substantial.”

Now that CRISPR technology has been validated in P falciparum, Dr Niles expects many scientists will adopt it for genetic studies of the parasite. Such efforts could reveal more about how the parasite invades red blood cells and replicates inside cells, which could generate new drug and vaccine targets.

“I think the impact could be quite huge,” he said. “It lowers the barrier to really being more imaginative in terms of how we do experiments and the kinds of questions that we can ask.”

Study authors Jacquin Niles

(left) and Jeffrey Wagner

Credit: Bryce Vickmark

The gene-editing technique CRISPR can disrupt a single gene from the malaria parasite Plasmodium falciparum in a matter of weeks, a new study suggests.

Although CRISPR’s success rate ranged from 50% to 100%, the researchers believe the technique shows promise and could greatly speed up gene analysis.

At present, it can take up to a year to determine the function of a single gene in P falciparum, which can hinder efforts to develop drugs and vaccines.

“Even though we’ve sequenced the entire genome of Plasmodium falciparum, half of it still remains functionally uncharacterized,” said Jacquin Niles, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.

“That’s about 2500 genes that, if only we knew what they did, we could think about novel therapeutics, whether it’s drugs or vaccines.”

Dr Niles and his colleagues described their use of CRISPR in P falciparum in Nature Methods.

The team noted that, in P falciparum, gene editing can take up to a year because it relies on homologous recombination, a type of genetic swapping that cells use to repair broken DNA strands and that occurs very rarely in the genome of the malaria parasite.

“You have to rely on this really inefficient process that occurs only if you have spontaneous DNA strand breaks that happen to fall within your region of interest,” Dr Niles said.

More recently, researchers have successfully used zinc finger nucleases to cut out specific genes, but this approach is costly because it requires a new nuclease to be designed for each gene target.

CRISPR exploits a set of bacterial proteins that protect microbes from viral infection. The system includes a DNA-cutting enzyme, Cas9, bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. This approach allows scientists to target and delete any gene by simply changing the RNA guide strand sequence.

As soon as researchers proved this system could work in cells other than bacteria, Dr Niles started to think about using it to manipulate P falciparum.

To test this approach, he and his colleagues tried using CRISPR to disrupt 2 genes, kahrp and eba-175, that had previously been knocked out in malaria using traditional approaches.

The kahrp gene produces a protein that causes red blood cells to develop a knobby appearance when infected with malaria. Dr Niles’s team was able to disrupt this gene in 100% of parasites treated with the CRISPR system. The red blood cells infected by parasites remained smooth.

The other gene, eba-175, codes for a protein that binds to red blood cell receptors and helps the malaria parasite enter cells. The researchers were only able to disrupt this gene in 50% to 80% of parasites manipulated with CRISPR.

“We consider this to be a win,” Dr Niles said. “Compared to the efficiency with which P falciparum genetics have been done in the past, even 50% is pretty substantial.”

Now that CRISPR technology has been validated in P falciparum, Dr Niles expects many scientists will adopt it for genetic studies of the parasite. Such efforts could reveal more about how the parasite invades red blood cells and replicates inside cells, which could generate new drug and vaccine targets.

“I think the impact could be quite huge,” he said. “It lowers the barrier to really being more imaginative in terms of how we do experiments and the kinds of questions that we can ask.”

Study authors Jacquin Niles

(left) and Jeffrey Wagner

Credit: Bryce Vickmark

The gene-editing technique CRISPR can disrupt a single gene from the malaria parasite Plasmodium falciparum in a matter of weeks, a new study suggests.

Although CRISPR’s success rate ranged from 50% to 100%, the researchers believe the technique shows promise and could greatly speed up gene analysis.

At present, it can take up to a year to determine the function of a single gene in P falciparum, which can hinder efforts to develop drugs and vaccines.

“Even though we’ve sequenced the entire genome of Plasmodium falciparum, half of it still remains functionally uncharacterized,” said Jacquin Niles, MD, PhD, of the Massachusetts Institute of Technology in Cambridge.

“That’s about 2500 genes that, if only we knew what they did, we could think about novel therapeutics, whether it’s drugs or vaccines.”

Dr Niles and his colleagues described their use of CRISPR in P falciparum in Nature Methods.

The team noted that, in P falciparum, gene editing can take up to a year because it relies on homologous recombination, a type of genetic swapping that cells use to repair broken DNA strands and that occurs very rarely in the genome of the malaria parasite.

“You have to rely on this really inefficient process that occurs only if you have spontaneous DNA strand breaks that happen to fall within your region of interest,” Dr Niles said.

More recently, researchers have successfully used zinc finger nucleases to cut out specific genes, but this approach is costly because it requires a new nuclease to be designed for each gene target.

CRISPR exploits a set of bacterial proteins that protect microbes from viral infection. The system includes a DNA-cutting enzyme, Cas9, bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. This approach allows scientists to target and delete any gene by simply changing the RNA guide strand sequence.

As soon as researchers proved this system could work in cells other than bacteria, Dr Niles started to think about using it to manipulate P falciparum.

To test this approach, he and his colleagues tried using CRISPR to disrupt 2 genes, kahrp and eba-175, that had previously been knocked out in malaria using traditional approaches.

The kahrp gene produces a protein that causes red blood cells to develop a knobby appearance when infected with malaria. Dr Niles’s team was able to disrupt this gene in 100% of parasites treated with the CRISPR system. The red blood cells infected by parasites remained smooth.

The other gene, eba-175, codes for a protein that binds to red blood cell receptors and helps the malaria parasite enter cells. The researchers were only able to disrupt this gene in 50% to 80% of parasites manipulated with CRISPR.

“We consider this to be a win,” Dr Niles said. “Compared to the efficiency with which P falciparum genetics have been done in the past, even 50% is pretty substantial.”

Now that CRISPR technology has been validated in P falciparum, Dr Niles expects many scientists will adopt it for genetic studies of the parasite. Such efforts could reveal more about how the parasite invades red blood cells and replicates inside cells, which could generate new drug and vaccine targets.

“I think the impact could be quite huge,” he said. “It lowers the barrier to really being more imaginative in terms of how we do experiments and the kinds of questions that we can ask.”

A hospitalist and SHM Public Policy Committee member is hopeful that SHM's recently released position paper recommending changes to the way the "observation status" designation is used for admitted hospital patients will help improve patient care.

The increasing use of the Centers for Medicare & Medicaid Services' (CMS) patient observation status designation—which grew 88% from 2006 to 2012—has frustrated hospitalists. Under the rule, patients are ineligible for skilled-nursing facility (SNF) care, may not claim insurance coverage for some medications, and may face uncertain cost-sharing and other financial liabilities for their hospitalization.

SHM outlined its concerns about the policy and suggested solutions in the report titled "The Observation Status Problem: Impact and Recommendations for Change."

CMS has attempted to address the issue by creating the "two-midnight rule." The report notes, however, that amid confusion on the application of the "two-midnight rule," Medicare auditing and enforcement have been pushed back several times, most recently to March 31, 2015.

"We still are unclear about what patient vulnerability is under this," says SHM Public Policy Committee member Ann Sheehy, MD, MS, FHM, a hospitalist at the University of Wisconsin School of Medicine and Public Health in Madison, who testified before Congress last May on observation status and other Medicare policies.

"We know that patients can't get SNF coverage when they're under observation," Dr. Sheehy says. "We know that patients are subject to unlimited co-pays when they're under observation, as opposed to when they're hospitalized as inpatients under Medicare Part A, which has a one-time deductible."

The SHM white paper outlines both short- and long-term fixes to the policy. In the near term, SHM recommends:

• Educating providers and patients on the purpose of observation status and raising confidence in when and how it should be applied;

• Changing SNF coverage rules to ensure patients’ eligibility; and

• Reforming the Medicare Recovery Audit Contractor program to improve RAC performance and reduce unintended pressures on admission decisions.

In the long term, the report suggests creating modifiers for diagnosis-related group (DRG) payments to assign to patients needing lower-acuity services, as well as crafting a list of DRGs to assign to patients needing short periods of inpatient care.

"The policy overall is very frustrating," Dr. Sheehy adds. "We hope that any rule change that comes out will address the core problems of observation so that patients can get the care they need with fair and appropriate insurance coverage." TH

Visit our website for more information about patient observation status.

A hospitalist and SHM Public Policy Committee member is hopeful that SHM's recently released position paper recommending changes to the way the "observation status" designation is used for admitted hospital patients will help improve patient care.

The increasing use of the Centers for Medicare & Medicaid Services' (CMS) patient observation status designation—which grew 88% from 2006 to 2012—has frustrated hospitalists. Under the rule, patients are ineligible for skilled-nursing facility (SNF) care, may not claim insurance coverage for some medications, and may face uncertain cost-sharing and other financial liabilities for their hospitalization.

SHM outlined its concerns about the policy and suggested solutions in the report titled "The Observation Status Problem: Impact and Recommendations for Change."

CMS has attempted to address the issue by creating the "two-midnight rule." The report notes, however, that amid confusion on the application of the "two-midnight rule," Medicare auditing and enforcement have been pushed back several times, most recently to March 31, 2015.

"We still are unclear about what patient vulnerability is under this," says SHM Public Policy Committee member Ann Sheehy, MD, MS, FHM, a hospitalist at the University of Wisconsin School of Medicine and Public Health in Madison, who testified before Congress last May on observation status and other Medicare policies.

"We know that patients can't get SNF coverage when they're under observation," Dr. Sheehy says. "We know that patients are subject to unlimited co-pays when they're under observation, as opposed to when they're hospitalized as inpatients under Medicare Part A, which has a one-time deductible."

The SHM white paper outlines both short- and long-term fixes to the policy. In the near term, SHM recommends:

• Educating providers and patients on the purpose of observation status and raising confidence in when and how it should be applied;

• Changing SNF coverage rules to ensure patients’ eligibility; and

• Reforming the Medicare Recovery Audit Contractor program to improve RAC performance and reduce unintended pressures on admission decisions.

In the long term, the report suggests creating modifiers for diagnosis-related group (DRG) payments to assign to patients needing lower-acuity services, as well as crafting a list of DRGs to assign to patients needing short periods of inpatient care.

"The policy overall is very frustrating," Dr. Sheehy adds. "We hope that any rule change that comes out will address the core problems of observation so that patients can get the care they need with fair and appropriate insurance coverage." TH

Visit our website for more information about patient observation status.

A hospitalist and SHM Public Policy Committee member is hopeful that SHM's recently released position paper recommending changes to the way the "observation status" designation is used for admitted hospital patients will help improve patient care.

The increasing use of the Centers for Medicare & Medicaid Services' (CMS) patient observation status designation—which grew 88% from 2006 to 2012—has frustrated hospitalists. Under the rule, patients are ineligible for skilled-nursing facility (SNF) care, may not claim insurance coverage for some medications, and may face uncertain cost-sharing and other financial liabilities for their hospitalization.

SHM outlined its concerns about the policy and suggested solutions in the report titled "The Observation Status Problem: Impact and Recommendations for Change."

CMS has attempted to address the issue by creating the "two-midnight rule." The report notes, however, that amid confusion on the application of the "two-midnight rule," Medicare auditing and enforcement have been pushed back several times, most recently to March 31, 2015.

"We still are unclear about what patient vulnerability is under this," says SHM Public Policy Committee member Ann Sheehy, MD, MS, FHM, a hospitalist at the University of Wisconsin School of Medicine and Public Health in Madison, who testified before Congress last May on observation status and other Medicare policies.

"We know that patients can't get SNF coverage when they're under observation," Dr. Sheehy says. "We know that patients are subject to unlimited co-pays when they're under observation, as opposed to when they're hospitalized as inpatients under Medicare Part A, which has a one-time deductible."

The SHM white paper outlines both short- and long-term fixes to the policy. In the near term, SHM recommends:

• Educating providers and patients on the purpose of observation status and raising confidence in when and how it should be applied;

• Changing SNF coverage rules to ensure patients’ eligibility; and

• Reforming the Medicare Recovery Audit Contractor program to improve RAC performance and reduce unintended pressures on admission decisions.

In the long term, the report suggests creating modifiers for diagnosis-related group (DRG) payments to assign to patients needing lower-acuity services, as well as crafting a list of DRGs to assign to patients needing short periods of inpatient care.

"The policy overall is very frustrating," Dr. Sheehy adds. "We hope that any rule change that comes out will address the core problems of observation so that patients can get the care they need with fair and appropriate insurance coverage." TH

Visit our website for more information about patient observation status.

In a Senate subcommittee hearing last month, a panel of patient safety experts and physicians raised concerns about the problem of preventable medical errors, which they say can be linked to more than 1,000 patient deaths per day.

For their part, SHM Public Policy Committee member Bradley Flansbaum, DO, MPH, FHM, says hospitalists should demand that their hospitals report better data on patient outcomes.

"When you talk about a patient death, you're talking about the efforts of an entire hospital going into the death or survival of that patient," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York. "If you ask, 'Where did something go wrong?' just looking at the mortality rate doesn't help. What service are you inquiring about? How can you get clean data that’s also useful to the clinician?"

In his testimony before the Subcommittee on Primary Health and Aging, hospitalist Ashish Jha, MD, MPH, referenced a landmark 1999 report from the Institute of Medicine (IOM), "To Err Is Human: Building a Safer Health System," [PDF] which estimated that between 44,000 and 98,000 deaths in the U.S. each year can be attributed to preventable medical errors.

Since the IOM report was published, little has been done to change the systems of care delivery that can lead providers to make errors, said Dr. Jha, an internist at the VA Boston Healthcare System and professor of health policy and management at the Harvard School of Public Health in Boston.

"When a physician orders the wrong medication because two drugs might sound alike, or when a patient develops a central-line infection because a rushed surgeon didn't use proper sterile technique, we now understand that we need to focus on the system that produced the errors," Dr. Jha told Senate subcommittee members.

Both Dr. Jha and panelist Peter Pronovost, MD, PhD, FCCM, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, said the Centers for Disease Control and Prevention should expand its National Nosocomial Infections Surveillance Program to collect and report data on medical errors.

Several other speakers said hospitals should be mandated to publicly report medical errors.

"Public disclosure is a critical element to preventing these events from happening," said panelist Lisa McGiffert, director of the Consumers Union Safe Patient Project in Austin, Texas. "It informs people about healthcare outcomes and motivates healthcare providers to do more to prevent errors." TH

Visit our website for more information on the impact of medical errors.

In a Senate subcommittee hearing last month, a panel of patient safety experts and physicians raised concerns about the problem of preventable medical errors, which they say can be linked to more than 1,000 patient deaths per day.

For their part, SHM Public Policy Committee member Bradley Flansbaum, DO, MPH, FHM, says hospitalists should demand that their hospitals report better data on patient outcomes.

"When you talk about a patient death, you're talking about the efforts of an entire hospital going into the death or survival of that patient," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York. "If you ask, 'Where did something go wrong?' just looking at the mortality rate doesn't help. What service are you inquiring about? How can you get clean data that’s also useful to the clinician?"

In his testimony before the Subcommittee on Primary Health and Aging, hospitalist Ashish Jha, MD, MPH, referenced a landmark 1999 report from the Institute of Medicine (IOM), "To Err Is Human: Building a Safer Health System," [PDF] which estimated that between 44,000 and 98,000 deaths in the U.S. each year can be attributed to preventable medical errors.

Since the IOM report was published, little has been done to change the systems of care delivery that can lead providers to make errors, said Dr. Jha, an internist at the VA Boston Healthcare System and professor of health policy and management at the Harvard School of Public Health in Boston.

"When a physician orders the wrong medication because two drugs might sound alike, or when a patient develops a central-line infection because a rushed surgeon didn't use proper sterile technique, we now understand that we need to focus on the system that produced the errors," Dr. Jha told Senate subcommittee members.

Both Dr. Jha and panelist Peter Pronovost, MD, PhD, FCCM, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, said the Centers for Disease Control and Prevention should expand its National Nosocomial Infections Surveillance Program to collect and report data on medical errors.

Several other speakers said hospitals should be mandated to publicly report medical errors.

"Public disclosure is a critical element to preventing these events from happening," said panelist Lisa McGiffert, director of the Consumers Union Safe Patient Project in Austin, Texas. "It informs people about healthcare outcomes and motivates healthcare providers to do more to prevent errors." TH

Visit our website for more information on the impact of medical errors.

In a Senate subcommittee hearing last month, a panel of patient safety experts and physicians raised concerns about the problem of preventable medical errors, which they say can be linked to more than 1,000 patient deaths per day.

For their part, SHM Public Policy Committee member Bradley Flansbaum, DO, MPH, FHM, says hospitalists should demand that their hospitals report better data on patient outcomes.

"When you talk about a patient death, you're talking about the efforts of an entire hospital going into the death or survival of that patient," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York. "If you ask, 'Where did something go wrong?' just looking at the mortality rate doesn't help. What service are you inquiring about? How can you get clean data that’s also useful to the clinician?"

In his testimony before the Subcommittee on Primary Health and Aging, hospitalist Ashish Jha, MD, MPH, referenced a landmark 1999 report from the Institute of Medicine (IOM), "To Err Is Human: Building a Safer Health System," [PDF] which estimated that between 44,000 and 98,000 deaths in the U.S. each year can be attributed to preventable medical errors.

Since the IOM report was published, little has been done to change the systems of care delivery that can lead providers to make errors, said Dr. Jha, an internist at the VA Boston Healthcare System and professor of health policy and management at the Harvard School of Public Health in Boston.

"When a physician orders the wrong medication because two drugs might sound alike, or when a patient develops a central-line infection because a rushed surgeon didn't use proper sterile technique, we now understand that we need to focus on the system that produced the errors," Dr. Jha told Senate subcommittee members.

Both Dr. Jha and panelist Peter Pronovost, MD, PhD, FCCM, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, said the Centers for Disease Control and Prevention should expand its National Nosocomial Infections Surveillance Program to collect and report data on medical errors.

Several other speakers said hospitals should be mandated to publicly report medical errors.

"Public disclosure is a critical element to preventing these events from happening," said panelist Lisa McGiffert, director of the Consumers Union Safe Patient Project in Austin, Texas. "It informs people about healthcare outcomes and motivates healthcare providers to do more to prevent errors." TH

Visit our website for more information on the impact of medical errors.

A majority of general surgery residents seriously consider dropping out of their training, with female residents more likely to consider quitting, a new study in JAMA Surgery reveals.

According to a survey, 58.0% of the 288 respondents "seriously considered leaving training." The most frequent reasons cited for wanting to quit training were sleep deprivation on a specific rotation (50%), an undesirable future lifestyle (47%), and excessive work hours on a specific rotation (41.4%). Survey results were published online July 30 in JAMA Surgery (2014 [doi:10.1001/jamasurg.2014.935]).

© Maridav / iStockphoto.com

Factors cited that ultimately keep general surgery residents from ending training are support from family or significant other (65%), support from other residents (63.5%), and perception of being better rested (58.9%).

"We believe that our survey findings highlight the fact that a desire to leave training may not be affected by job rigor alone but rather [by] program-specific or rotation-specific factors or dissatisfaction with a future career in general surgery," the report states. Dr. Edward Gifford of the department of surgery, University of California, Los Angeles, Medical Center, is the report’s lead author.

In addressing the factors that led to consideration for leaving training, the authors noted that "a potential remedy may be to identify those high work-hour rotations and modify them accordingly," though lifestyle concerns may be harder to address as practicing surgeons "continue to experience high levels of work-home conflicts and burnout."

For women specifically, another issue is "the paucity of female mentors in academic surgery," the report states. "Striving to increase the number of female faculty members within training programs and refining the mentor-mentee relationship with incoming residents may improve the outlook and productivity of future female surgeons."

Overall, while men’s thoughts of quitting decreased as their residency progressed, women’s considerations remained persistent. The report cites previous studies that reported that men and women view general surgery careers differently, including that it was not a welcoming career because of lifestyle challenges, particularly if the woman had children, limited flexible training, and lack of role models.

"These findings may explain why women in our survey continued to consider leaving residency throughout the duration of training and underscores the importance of supporting female residents through the difficult balance between motherhood and professional life," the report states.

The study was approved by the human subjects committee of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles. The authors reported no conflicts of interest.

A majority of general surgery residents seriously consider dropping out of their training, with female residents more likely to consider quitting, a new study in JAMA Surgery reveals.

According to a survey, 58.0% of the 288 respondents "seriously considered leaving training." The most frequent reasons cited for wanting to quit training were sleep deprivation on a specific rotation (50%), an undesirable future lifestyle (47%), and excessive work hours on a specific rotation (41.4%). Survey results were published online July 30 in JAMA Surgery (2014 [doi:10.1001/jamasurg.2014.935]).

© Maridav / iStockphoto.com

Factors cited that ultimately keep general surgery residents from ending training are support from family or significant other (65%), support from other residents (63.5%), and perception of being better rested (58.9%).

"We believe that our survey findings highlight the fact that a desire to leave training may not be affected by job rigor alone but rather [by] program-specific or rotation-specific factors or dissatisfaction with a future career in general surgery," the report states. Dr. Edward Gifford of the department of surgery, University of California, Los Angeles, Medical Center, is the report’s lead author.

In addressing the factors that led to consideration for leaving training, the authors noted that "a potential remedy may be to identify those high work-hour rotations and modify them accordingly," though lifestyle concerns may be harder to address as practicing surgeons "continue to experience high levels of work-home conflicts and burnout."

For women specifically, another issue is "the paucity of female mentors in academic surgery," the report states. "Striving to increase the number of female faculty members within training programs and refining the mentor-mentee relationship with incoming residents may improve the outlook and productivity of future female surgeons."

Overall, while men’s thoughts of quitting decreased as their residency progressed, women’s considerations remained persistent. The report cites previous studies that reported that men and women view general surgery careers differently, including that it was not a welcoming career because of lifestyle challenges, particularly if the woman had children, limited flexible training, and lack of role models.

"These findings may explain why women in our survey continued to consider leaving residency throughout the duration of training and underscores the importance of supporting female residents through the difficult balance between motherhood and professional life," the report states.

The study was approved by the human subjects committee of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles. The authors reported no conflicts of interest.

A majority of general surgery residents seriously consider dropping out of their training, with female residents more likely to consider quitting, a new study in JAMA Surgery reveals.

According to a survey, 58.0% of the 288 respondents "seriously considered leaving training." The most frequent reasons cited for wanting to quit training were sleep deprivation on a specific rotation (50%), an undesirable future lifestyle (47%), and excessive work hours on a specific rotation (41.4%). Survey results were published online July 30 in JAMA Surgery (2014 [doi:10.1001/jamasurg.2014.935]).

© Maridav / iStockphoto.com

Factors cited that ultimately keep general surgery residents from ending training are support from family or significant other (65%), support from other residents (63.5%), and perception of being better rested (58.9%).

"We believe that our survey findings highlight the fact that a desire to leave training may not be affected by job rigor alone but rather [by] program-specific or rotation-specific factors or dissatisfaction with a future career in general surgery," the report states. Dr. Edward Gifford of the department of surgery, University of California, Los Angeles, Medical Center, is the report’s lead author.

In addressing the factors that led to consideration for leaving training, the authors noted that "a potential remedy may be to identify those high work-hour rotations and modify them accordingly," though lifestyle concerns may be harder to address as practicing surgeons "continue to experience high levels of work-home conflicts and burnout."

For women specifically, another issue is "the paucity of female mentors in academic surgery," the report states. "Striving to increase the number of female faculty members within training programs and refining the mentor-mentee relationship with incoming residents may improve the outlook and productivity of future female surgeons."

Overall, while men’s thoughts of quitting decreased as their residency progressed, women’s considerations remained persistent. The report cites previous studies that reported that men and women view general surgery careers differently, including that it was not a welcoming career because of lifestyle challenges, particularly if the woman had children, limited flexible training, and lack of role models.

"These findings may explain why women in our survey continued to consider leaving residency throughout the duration of training and underscores the importance of supporting female residents through the difficult balance between motherhood and professional life," the report states.

The study was approved by the human subjects committee of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles. The authors reported no conflicts of interest.

An estimated 42 million (18.1%) of the U.S. adult population continues to smoke cigarettes. Effective treatments exist for patients who are willing to avail themselves of such assistance. Varenicline is one of the most effective medications that we have to combat tobacco dependence. However, it doesn’t work for everybody, and questions have remained about how safe and effective it is to combine varenicline with other smoking cessation therapies such as nicotine replacement therapy.

Varenicline binds to a specific nicotine receptor, thereby partially agonizing and blocking it. The result is decreased cravings for tobacco and increased smoking quit rates. Data from early studies conducted by our group suggested that nicotine replacement therapy (NRT) combined with varenicline was safe, but questions remained about its efficacy.

One group of researchers conducted a multicenter clinical trial evaluating the efficacy of combining varenicline and the nicotine patch for increasing smoking cessation rates. Smokers were eligible if they smoked at least 10 cigarettes per day, reported F.N. Coenraad, from the Stellenbosch University, Cape Town, South Africa, and associates. Participants were randomized to active 15-mg nicotine patches or placebo patches started 2 weeks before the target quit date. All participants received varenicline for a total of 14 weeks with a 1-week ramp-up and a 1-week taper. Use of the varenicline in combination with the nicotine patch resulted in increased rates of continuous abstinence from smoking at 12 weeks (no smoking from weeks 9 to 12: 55.4% vs. 40.9%; odds ratio, 1.85; 95% confidence interval, 1.19-2.89; P = .007) and at 24 weeks (no smoking from weeks 9 to 24: 49% vs. 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) (JAMA 2014;312:155-61).

This is a fantastic study answering a lingering question in tobacco control. But what is the theoretical underpinning by which this combination works? Isn’t the NRT blocked by the varenicline? It is possible that the varenicline incompletely saturates the nicotine receptors, which are additionally saturated by the supplemented nicotine. The varenicline effect is mediated through the alpha-4 beta-2 nicotinic receptor, and it is also possible that nicotine binds to nicotine receptor types that varenicline does not bind to, which decreases withdrawal symptoms.

We aren’t exactly sure how this might be working, but a near doubling of the odds of quitting is not to be disregarded. We are also not sure whether the effect holds when one uses other types of NRT such as the nicotine inhaler, nicotine lozenge, nicotine nasal spray, and nicotine gum. In practice, I tend to lean toward a combination of varenicline with the nicotine inhaler since the inhaler can help with some of the behavioral aspects of smoking while the varenicline does its heavy lifting.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. Dr. Ebbert reports receiving research support from Pfizer, manufacturer of varenicline and the nicotine inhaler, and consulting fees from GlaxoSmithKline, manufacturer of the nicotine patch. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

An estimated 42 million (18.1%) of the U.S. adult population continues to smoke cigarettes. Effective treatments exist for patients who are willing to avail themselves of such assistance. Varenicline is one of the most effective medications that we have to combat tobacco dependence. However, it doesn’t work for everybody, and questions have remained about how safe and effective it is to combine varenicline with other smoking cessation therapies such as nicotine replacement therapy.

Varenicline binds to a specific nicotine receptor, thereby partially agonizing and blocking it. The result is decreased cravings for tobacco and increased smoking quit rates. Data from early studies conducted by our group suggested that nicotine replacement therapy (NRT) combined with varenicline was safe, but questions remained about its efficacy.

One group of researchers conducted a multicenter clinical trial evaluating the efficacy of combining varenicline and the nicotine patch for increasing smoking cessation rates. Smokers were eligible if they smoked at least 10 cigarettes per day, reported F.N. Coenraad, from the Stellenbosch University, Cape Town, South Africa, and associates. Participants were randomized to active 15-mg nicotine patches or placebo patches started 2 weeks before the target quit date. All participants received varenicline for a total of 14 weeks with a 1-week ramp-up and a 1-week taper. Use of the varenicline in combination with the nicotine patch resulted in increased rates of continuous abstinence from smoking at 12 weeks (no smoking from weeks 9 to 12: 55.4% vs. 40.9%; odds ratio, 1.85; 95% confidence interval, 1.19-2.89; P = .007) and at 24 weeks (no smoking from weeks 9 to 24: 49% vs. 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) (JAMA 2014;312:155-61).

This is a fantastic study answering a lingering question in tobacco control. But what is the theoretical underpinning by which this combination works? Isn’t the NRT blocked by the varenicline? It is possible that the varenicline incompletely saturates the nicotine receptors, which are additionally saturated by the supplemented nicotine. The varenicline effect is mediated through the alpha-4 beta-2 nicotinic receptor, and it is also possible that nicotine binds to nicotine receptor types that varenicline does not bind to, which decreases withdrawal symptoms.

We aren’t exactly sure how this might be working, but a near doubling of the odds of quitting is not to be disregarded. We are also not sure whether the effect holds when one uses other types of NRT such as the nicotine inhaler, nicotine lozenge, nicotine nasal spray, and nicotine gum. In practice, I tend to lean toward a combination of varenicline with the nicotine inhaler since the inhaler can help with some of the behavioral aspects of smoking while the varenicline does its heavy lifting.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. Dr. Ebbert reports receiving research support from Pfizer, manufacturer of varenicline and the nicotine inhaler, and consulting fees from GlaxoSmithKline, manufacturer of the nicotine patch. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

An estimated 42 million (18.1%) of the U.S. adult population continues to smoke cigarettes. Effective treatments exist for patients who are willing to avail themselves of such assistance. Varenicline is one of the most effective medications that we have to combat tobacco dependence. However, it doesn’t work for everybody, and questions have remained about how safe and effective it is to combine varenicline with other smoking cessation therapies such as nicotine replacement therapy.

Varenicline binds to a specific nicotine receptor, thereby partially agonizing and blocking it. The result is decreased cravings for tobacco and increased smoking quit rates. Data from early studies conducted by our group suggested that nicotine replacement therapy (NRT) combined with varenicline was safe, but questions remained about its efficacy.

One group of researchers conducted a multicenter clinical trial evaluating the efficacy of combining varenicline and the nicotine patch for increasing smoking cessation rates. Smokers were eligible if they smoked at least 10 cigarettes per day, reported F.N. Coenraad, from the Stellenbosch University, Cape Town, South Africa, and associates. Participants were randomized to active 15-mg nicotine patches or placebo patches started 2 weeks before the target quit date. All participants received varenicline for a total of 14 weeks with a 1-week ramp-up and a 1-week taper. Use of the varenicline in combination with the nicotine patch resulted in increased rates of continuous abstinence from smoking at 12 weeks (no smoking from weeks 9 to 12: 55.4% vs. 40.9%; odds ratio, 1.85; 95% confidence interval, 1.19-2.89; P = .007) and at 24 weeks (no smoking from weeks 9 to 24: 49% vs. 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) (JAMA 2014;312:155-61).

This is a fantastic study answering a lingering question in tobacco control. But what is the theoretical underpinning by which this combination works? Isn’t the NRT blocked by the varenicline? It is possible that the varenicline incompletely saturates the nicotine receptors, which are additionally saturated by the supplemented nicotine. The varenicline effect is mediated through the alpha-4 beta-2 nicotinic receptor, and it is also possible that nicotine binds to nicotine receptor types that varenicline does not bind to, which decreases withdrawal symptoms.

We aren’t exactly sure how this might be working, but a near doubling of the odds of quitting is not to be disregarded. We are also not sure whether the effect holds when one uses other types of NRT such as the nicotine inhaler, nicotine lozenge, nicotine nasal spray, and nicotine gum. In practice, I tend to lean toward a combination of varenicline with the nicotine inhaler since the inhaler can help with some of the behavioral aspects of smoking while the varenicline does its heavy lifting.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. Dr. Ebbert reports receiving research support from Pfizer, manufacturer of varenicline and the nicotine inhaler, and consulting fees from GlaxoSmithKline, manufacturer of the nicotine patch. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

A device that preserves less-than-ideal donor lungs until they are cleared for transplantation has been approved, the Food and Drug Administration announced on Aug. 12.

The ex vivo perfusion device preserves donated lungs that initially do not meet all the criteria for a transplantable lung. The device does this by warming the donor lung to "near normal body temperature," continuously flushing the lung with a sterile solution, and ventilating the lungs, "which oxygenates the cells and makes it possible for the transplant team to examine the lungs’ airways with a bronchoscope," according to the FDA statement.

Courtesy XVIVO Perfusion

The lungs can remain in the machine for up to 4 hours, providing time for the transplant team to evaluate the lungs to determine if they meet the criteria; donor lungs that meet the criteria are then transplanted into a patient.

The device, the XVIVO Perfusion System (XPS) with STEEN Solution, is manufactured by XVIVO Perfusion.

"With this approval, there may be more lungs available for transplant, which could allow more people with end stage lung disease who have exhausted all other treatment options to be able to receive a lung transplant," Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, Silver Spring, Md., said in the statement.

About one in five donor lungs meet the standard transplantation criteria. In the United States, 1,754 lung transplants were performed in 2012 and 1,616 potential recipients were on the lung transplant waiting list at the end of 2012, according to the FDA.

In two studies, outcomes for lung-transplant recipients were similar among those who received a donor lung preserved with the device and those who received donor lungs that were considered ideal and were preserved in cold storage. "Both trials showed that recipients of the ideal and non-ideal lungs had similar survival rates up to 12 months after transplant and similar rates of organ rejection," the FDA statement said.

The manufacturer is required to conduct a long-term study of the effects of the device as a condition of approval.

[email protected]

A device that preserves less-than-ideal donor lungs until they are cleared for transplantation has been approved, the Food and Drug Administration announced on Aug. 12.

The ex vivo perfusion device preserves donated lungs that initially do not meet all the criteria for a transplantable lung. The device does this by warming the donor lung to "near normal body temperature," continuously flushing the lung with a sterile solution, and ventilating the lungs, "which oxygenates the cells and makes it possible for the transplant team to examine the lungs’ airways with a bronchoscope," according to the FDA statement.

Courtesy XVIVO Perfusion

The lungs can remain in the machine for up to 4 hours, providing time for the transplant team to evaluate the lungs to determine if they meet the criteria; donor lungs that meet the criteria are then transplanted into a patient.

The device, the XVIVO Perfusion System (XPS) with STEEN Solution, is manufactured by XVIVO Perfusion.

"With this approval, there may be more lungs available for transplant, which could allow more people with end stage lung disease who have exhausted all other treatment options to be able to receive a lung transplant," Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, Silver Spring, Md., said in the statement.

About one in five donor lungs meet the standard transplantation criteria. In the United States, 1,754 lung transplants were performed in 2012 and 1,616 potential recipients were on the lung transplant waiting list at the end of 2012, according to the FDA.

In two studies, outcomes for lung-transplant recipients were similar among those who received a donor lung preserved with the device and those who received donor lungs that were considered ideal and were preserved in cold storage. "Both trials showed that recipients of the ideal and non-ideal lungs had similar survival rates up to 12 months after transplant and similar rates of organ rejection," the FDA statement said.

The manufacturer is required to conduct a long-term study of the effects of the device as a condition of approval.

[email protected]

A device that preserves less-than-ideal donor lungs until they are cleared for transplantation has been approved, the Food and Drug Administration announced on Aug. 12.

The ex vivo perfusion device preserves donated lungs that initially do not meet all the criteria for a transplantable lung. The device does this by warming the donor lung to "near normal body temperature," continuously flushing the lung with a sterile solution, and ventilating the lungs, "which oxygenates the cells and makes it possible for the transplant team to examine the lungs’ airways with a bronchoscope," according to the FDA statement.

Courtesy XVIVO Perfusion

The lungs can remain in the machine for up to 4 hours, providing time for the transplant team to evaluate the lungs to determine if they meet the criteria; donor lungs that meet the criteria are then transplanted into a patient.

The device, the XVIVO Perfusion System (XPS) with STEEN Solution, is manufactured by XVIVO Perfusion.

"With this approval, there may be more lungs available for transplant, which could allow more people with end stage lung disease who have exhausted all other treatment options to be able to receive a lung transplant," Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, Silver Spring, Md., said in the statement.

About one in five donor lungs meet the standard transplantation criteria. In the United States, 1,754 lung transplants were performed in 2012 and 1,616 potential recipients were on the lung transplant waiting list at the end of 2012, according to the FDA.

In two studies, outcomes for lung-transplant recipients were similar among those who received a donor lung preserved with the device and those who received donor lungs that were considered ideal and were preserved in cold storage. "Both trials showed that recipients of the ideal and non-ideal lungs had similar survival rates up to 12 months after transplant and similar rates of organ rejection," the FDA statement said.

The manufacturer is required to conduct a long-term study of the effects of the device as a condition of approval.

[email protected]