Offering palliative care early to hospitalized patients with multiple serious conditions could improve care and help reduce healthcare spending, according to “Palliative Care Teams’ Cost-Saving Effect Is Larger for Cancer Patients with Higher Numbers of Comorbidities,” published in Health Affairs. When adults with advanced cancer (excluding those with dementia) received a palliative care consultation within two days of admission, costs were 22% lower for patients with a comorbidity score of 2 to 3 and 32% lower for those with a score of 4 or higher.

Reference

1. May P, Garrido MM, Cassel JB, et al. Palliative care teams’ cost-saving effect is larger for cancer patients with higher numbers of comorbidities. Health Aff. 2016;35(1):44-53.

Quick Byte

Efforts to shift provider payment from fee-for-service to more risk-based alternatives are proceeding slowly: Nearly 95% of all 2013 physician office visits were reimbursed as fee-for-service.

Reference

1. Zuvekas SH, Cohen JW. Fee-for-service, while much maligned, remains the dominant payment method for physician visits. Health Aff. 2016;35(3):411-414. doi:10.1377/hlthaff.2015.1291.

Offering palliative care early to hospitalized patients with multiple serious conditions could improve care and help reduce healthcare spending, according to “Palliative Care Teams’ Cost-Saving Effect Is Larger for Cancer Patients with Higher Numbers of Comorbidities,” published in Health Affairs. When adults with advanced cancer (excluding those with dementia) received a palliative care consultation within two days of admission, costs were 22% lower for patients with a comorbidity score of 2 to 3 and 32% lower for those with a score of 4 or higher.

Reference

1. May P, Garrido MM, Cassel JB, et al. Palliative care teams’ cost-saving effect is larger for cancer patients with higher numbers of comorbidities. Health Aff. 2016;35(1):44-53.

Quick Byte

Efforts to shift provider payment from fee-for-service to more risk-based alternatives are proceeding slowly: Nearly 95% of all 2013 physician office visits were reimbursed as fee-for-service.

Reference

1. Zuvekas SH, Cohen JW. Fee-for-service, while much maligned, remains the dominant payment method for physician visits. Health Aff. 2016;35(3):411-414. doi:10.1377/hlthaff.2015.1291.

Offering palliative care early to hospitalized patients with multiple serious conditions could improve care and help reduce healthcare spending, according to “Palliative Care Teams’ Cost-Saving Effect Is Larger for Cancer Patients with Higher Numbers of Comorbidities,” published in Health Affairs. When adults with advanced cancer (excluding those with dementia) received a palliative care consultation within two days of admission, costs were 22% lower for patients with a comorbidity score of 2 to 3 and 32% lower for those with a score of 4 or higher.

Reference

1. May P, Garrido MM, Cassel JB, et al. Palliative care teams’ cost-saving effect is larger for cancer patients with higher numbers of comorbidities. Health Aff. 2016;35(1):44-53.

Quick Byte

Efforts to shift provider payment from fee-for-service to more risk-based alternatives are proceeding slowly: Nearly 95% of all 2013 physician office visits were reimbursed as fee-for-service.

Reference

1. Zuvekas SH, Cohen JW. Fee-for-service, while much maligned, remains the dominant payment method for physician visits. Health Aff. 2016;35(3):411-414. doi:10.1377/hlthaff.2015.1291.

Alert emails can be a simple, low-cost means of improving quality in a hospital, as the Department of Medicine at Massachusetts General Hospital in Boston learned. The trial there is summarized in “Alert Emails Improve Quality in a Large Academic Hospitalist Group,” an abstract by Warren Chuang, MD, and Bijay Acharya, MD.

When each of the hospital’s divisions was asked to designate important quality goals, the Hospital Medicine Division chose pre-noon discharge rate and discharge summary completion timeliness. Group emails were deployed first: Monthly alerts went to the entire unit emphasizing target numbers, reporting the group’s current performance, and outlining future performance needed to meet the targets. This led to an improvement in discharge summary completion rate from 89.1% to 94.8%.

The same improvement was not seen in the pre-noon discharge rate, so the next step was to send individual emails to every attending whose pre-noon discharge rate was below target levels. This resulted in dramatic improvement: Having fallen to 16.0%, the rate rose to 19.5% after the email campaign.

The authors’ conclusion? Periodic individual email alerts that make individual performance transparent may prove to be the most effective way to achieve quality improvement in operational measures.

Reference

1. Chuang W, Acharya B. Alert emails improve quality in a large academic hospitalist group [abstract]. J Hosp Med. 2015;10(suppl2). Available at: http://www.shmabstracts.com/abstract/alert-emails-improve-quality-in-a-large-academic-hospitalist-group/. Accessed February 14, 2016.

Alert emails can be a simple, low-cost means of improving quality in a hospital, as the Department of Medicine at Massachusetts General Hospital in Boston learned. The trial there is summarized in “Alert Emails Improve Quality in a Large Academic Hospitalist Group,” an abstract by Warren Chuang, MD, and Bijay Acharya, MD.

When each of the hospital’s divisions was asked to designate important quality goals, the Hospital Medicine Division chose pre-noon discharge rate and discharge summary completion timeliness. Group emails were deployed first: Monthly alerts went to the entire unit emphasizing target numbers, reporting the group’s current performance, and outlining future performance needed to meet the targets. This led to an improvement in discharge summary completion rate from 89.1% to 94.8%.

The same improvement was not seen in the pre-noon discharge rate, so the next step was to send individual emails to every attending whose pre-noon discharge rate was below target levels. This resulted in dramatic improvement: Having fallen to 16.0%, the rate rose to 19.5% after the email campaign.

The authors’ conclusion? Periodic individual email alerts that make individual performance transparent may prove to be the most effective way to achieve quality improvement in operational measures.

Reference

1. Chuang W, Acharya B. Alert emails improve quality in a large academic hospitalist group [abstract]. J Hosp Med. 2015;10(suppl2). Available at: http://www.shmabstracts.com/abstract/alert-emails-improve-quality-in-a-large-academic-hospitalist-group/. Accessed February 14, 2016.

Alert emails can be a simple, low-cost means of improving quality in a hospital, as the Department of Medicine at Massachusetts General Hospital in Boston learned. The trial there is summarized in “Alert Emails Improve Quality in a Large Academic Hospitalist Group,” an abstract by Warren Chuang, MD, and Bijay Acharya, MD.

When each of the hospital’s divisions was asked to designate important quality goals, the Hospital Medicine Division chose pre-noon discharge rate and discharge summary completion timeliness. Group emails were deployed first: Monthly alerts went to the entire unit emphasizing target numbers, reporting the group’s current performance, and outlining future performance needed to meet the targets. This led to an improvement in discharge summary completion rate from 89.1% to 94.8%.

The same improvement was not seen in the pre-noon discharge rate, so the next step was to send individual emails to every attending whose pre-noon discharge rate was below target levels. This resulted in dramatic improvement: Having fallen to 16.0%, the rate rose to 19.5% after the email campaign.

The authors’ conclusion? Periodic individual email alerts that make individual performance transparent may prove to be the most effective way to achieve quality improvement in operational measures.

Reference

1. Chuang W, Acharya B. Alert emails improve quality in a large academic hospitalist group [abstract]. J Hosp Med. 2015;10(suppl2). Available at: http://www.shmabstracts.com/abstract/alert-emails-improve-quality-in-a-large-academic-hospitalist-group/. Accessed February 14, 2016.

Gut bacteria

A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.

Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.

The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.

Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.

A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.

So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.

The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.

Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.

The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)

The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.

Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.

“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.

“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”

Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.

“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.

Gut bacteria

A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.

Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.

The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.

Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.

A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.

So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.

The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.

Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.

The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)

The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.

Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.

“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.

“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”

Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.

“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.

Gut bacteria

A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.

Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.

The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.

Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.

A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.

So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.

The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.

Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.

The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)

The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.

Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.

“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.

“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”

Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.

“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.

The therapy is called “Memory and Attention Adaptation Training” (MAAT).

It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.

MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.

The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.

The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”

Both treatments were delivered over a videoconference network between health centers to minimize patient travel.

All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.

Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.

Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).

MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.

“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”

“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”

Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.

The therapy is called “Memory and Attention Adaptation Training” (MAAT).

It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.

MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.

The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.

The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”

Both treatments were delivered over a videoconference network between health centers to minimize patient travel.

All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.

Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.

Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).

MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.

“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”

“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”

Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.

The therapy is called “Memory and Attention Adaptation Training” (MAAT).

It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.

MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.

The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.

The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”

Both treatments were delivered over a videoconference network between health centers to minimize patient travel.

All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.

Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.

Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).

MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.

“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”

“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”

Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Drug release in a cancer cell

Image courtesy of PNAS

The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.

Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.

They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.

“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.

However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.

“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”

In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.

Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.

In one cell line, the team found a stark disagreement between the two metrics.

“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.

“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”

The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.

The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.

Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.

However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.

Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.

In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.

The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.

The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.

When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.

The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.

“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.

“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”

One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.

“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”

The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.

They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.

“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.

“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.

Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.

However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.

Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.

In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.

The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.

The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.

When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.

The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.

“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.

“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”

One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.

“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”

The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.

They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.

“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.

“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.

Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.

However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.

Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.

In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.

The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.

The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.

When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.

The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.

“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.

“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”

One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.

“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”

The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.

They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.

“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.

“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”

BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.

The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.

When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.

BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.

The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.

The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.

Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.

The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.

He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.

The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.

aotto@frontlinemedcom.com

BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.

The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.

When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.

BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.

The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.

The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.

Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.

The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.

He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.

The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.

aotto@frontlinemedcom.com

BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.

The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.

When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.

BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.

The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.

The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.

Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.

The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.

He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.

The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.

aotto@frontlinemedcom.com

Pimavanserin on April 29 became the first drug to receive approval from the Food and Drug Administration for the indication of hallucinations and delusions associated with psychosis in Parkinson’s disease.

The drug, to be marketed under the brand name Nuplazid by Acadia Pharmaceuticals, was shown in a 6-week clinical trial of 199 participants to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease.

The most common side effects reported from the clinical trial included peripheral edema, nausea, and confused state of mind.

“Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms,” said Dr. Mitchell Mathis, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research.

The FDA gave pimavanserin a Boxed Warning in relation to the general increased risk of death associated with the use of atypical antipsychotic drugs to treat older people with dementia-related psychosis. No other drug atypical antipsychotic drug has been approved to treat patients with dementia-related psychosis.

Read the agency’s full statement on the FDA website.

llaubach@frontlinemedcom.com

Pimavanserin on April 29 became the first drug to receive approval from the Food and Drug Administration for the indication of hallucinations and delusions associated with psychosis in Parkinson’s disease.

The drug, to be marketed under the brand name Nuplazid by Acadia Pharmaceuticals, was shown in a 6-week clinical trial of 199 participants to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease.

The most common side effects reported from the clinical trial included peripheral edema, nausea, and confused state of mind.

“Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms,” said Dr. Mitchell Mathis, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research.

The FDA gave pimavanserin a Boxed Warning in relation to the general increased risk of death associated with the use of atypical antipsychotic drugs to treat older people with dementia-related psychosis. No other drug atypical antipsychotic drug has been approved to treat patients with dementia-related psychosis.

Read the agency’s full statement on the FDA website.

llaubach@frontlinemedcom.com

Pimavanserin on April 29 became the first drug to receive approval from the Food and Drug Administration for the indication of hallucinations and delusions associated with psychosis in Parkinson’s disease.

The drug, to be marketed under the brand name Nuplazid by Acadia Pharmaceuticals, was shown in a 6-week clinical trial of 199 participants to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease.

The most common side effects reported from the clinical trial included peripheral edema, nausea, and confused state of mind.

“Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms,” said Dr. Mitchell Mathis, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research.

The FDA gave pimavanserin a Boxed Warning in relation to the general increased risk of death associated with the use of atypical antipsychotic drugs to treat older people with dementia-related psychosis. No other drug atypical antipsychotic drug has been approved to treat patients with dementia-related psychosis.

Read the agency’s full statement on the FDA website.

llaubach@frontlinemedcom.com

To the Editor:

Dermatofibroma is a common cutaneous lesion that most frequently affects young or middle-aged adults, especially women.¹ Clinically, it appears as a firm, pink or brown nodule. It may be painful or show a tendency for scarring. The pathognomonic feature of dermatofibroma, regarded as a fibrohistiocytic tumor, is the so-called button sign caused by skin depression following pressure. We present a unique case of elongated dermatofibroma with a linear, white, scarlike patch with a brownish pigmented network and globules.

A 40-year-old woman presented with a linear elongated lesion localized to the right side of the infrascapular region of 10 years’ duration. The lesion initially was a small brownish plaque. There was no history of trauma or scratching. Over the next 10 years, the lesion slowly progressed, finally becoming a linear, atrophic, brownish plaque that was 2.5-cm long (Figure 1). The button sign was positive. On dermoscopy the central, elongated, white patch was visualized not as a typical round patch but as a scarlike white line (Figure 2A) surrounded by a brownish network that was especially pronounced in the distal parts of the lesion. In the upper part of the lesion, multiple marginally disseminated, dark brown dots were present. Brownish globules within the linear white patch also were observed in the lower central part. Figure 2B presents a dermoscopic picture of the linear variant of dermatofibroma. For cosmetic reasons, the patient underwent total surgical excision of the lesion. Histopathology revealed distinct characteristics of dermatofibroma (Figures 3A and 3B).

The most common features of dermatofibromas seen in polarized and nonpolarized dermoscopy are central white scarlike patches, brown globulelike structures, vascular structures, and a peripheral fine pigmented network.² Kilinc Karaarslan et al³ described atypical dermatofibromas with linear irregular crypts, which were seen in 26.9% of all studied cases. These irregular crypts were mainly medium in size (10 lesions), with only 2 lesions being tiny and regularly distributed. Only one lesion had atypical clinical and dermoscopic features occurring as an atrophic plaque with multiple small scarlike areas and peripherally distributed pigment network.³ Based on this typology, we believe our patient represents a case of elongated dermatofibroma that could be an atrophic variant of dermatofibroma. This form would not appear as a small scarlike area with pigment network in a somewhat patchy distribution³ but as a scarlike linear chord with a bipolar pigment network. Zaballos et al¹ described 10 dermoscopic patterns of dermatofibroma (N=412); the most common was a central white patch and peripheral pigment network in approximately 35% of cases. A white scarlike patch was observed in 57.0% of dermat-ofibromas in 4 variants: (1) a solitary structure located in the center; (2) multiple white scarlike patches; (3) white scarlike patch extending throughout the lesion or irregularly distributed; and (4) white network (central, total, or irregular).¹ Agero et al² first described the new feature as a central white patch characterized by shiny white streaks. The most frequent dermoscopic pattern associated with dermatofibromas is the central white scarlike patch and peripheral delicate pigment network.^1,4 Arpaia et al⁴ observed that dermoscopic patterns may correspond to distinct sequential stages of the formation of dermatofibroma. The linear character we described may be related to a variant of scarring keloid dermatofibroma.⁵

To the Editor:

Dermatofibroma is a common cutaneous lesion that most frequently affects young or middle-aged adults, especially women.¹ Clinically, it appears as a firm, pink or brown nodule. It may be painful or show a tendency for scarring. The pathognomonic feature of dermatofibroma, regarded as a fibrohistiocytic tumor, is the so-called button sign caused by skin depression following pressure. We present a unique case of elongated dermatofibroma with a linear, white, scarlike patch with a brownish pigmented network and globules.

A 40-year-old woman presented with a linear elongated lesion localized to the right side of the infrascapular region of 10 years’ duration. The lesion initially was a small brownish plaque. There was no history of trauma or scratching. Over the next 10 years, the lesion slowly progressed, finally becoming a linear, atrophic, brownish plaque that was 2.5-cm long (Figure 1). The button sign was positive. On dermoscopy the central, elongated, white patch was visualized not as a typical round patch but as a scarlike white line (Figure 2A) surrounded by a brownish network that was especially pronounced in the distal parts of the lesion. In the upper part of the lesion, multiple marginally disseminated, dark brown dots were present. Brownish globules within the linear white patch also were observed in the lower central part. Figure 2B presents a dermoscopic picture of the linear variant of dermatofibroma. For cosmetic reasons, the patient underwent total surgical excision of the lesion. Histopathology revealed distinct characteristics of dermatofibroma (Figures 3A and 3B).

The most common features of dermatofibromas seen in polarized and nonpolarized dermoscopy are central white scarlike patches, brown globulelike structures, vascular structures, and a peripheral fine pigmented network.² Kilinc Karaarslan et al³ described atypical dermatofibromas with linear irregular crypts, which were seen in 26.9% of all studied cases. These irregular crypts were mainly medium in size (10 lesions), with only 2 lesions being tiny and regularly distributed. Only one lesion had atypical clinical and dermoscopic features occurring as an atrophic plaque with multiple small scarlike areas and peripherally distributed pigment network.³ Based on this typology, we believe our patient represents a case of elongated dermatofibroma that could be an atrophic variant of dermatofibroma. This form would not appear as a small scarlike area with pigment network in a somewhat patchy distribution³ but as a scarlike linear chord with a bipolar pigment network. Zaballos et al¹ described 10 dermoscopic patterns of dermatofibroma (N=412); the most common was a central white patch and peripheral pigment network in approximately 35% of cases. A white scarlike patch was observed in 57.0% of dermat-ofibromas in 4 variants: (1) a solitary structure located in the center; (2) multiple white scarlike patches; (3) white scarlike patch extending throughout the lesion or irregularly distributed; and (4) white network (central, total, or irregular).¹ Agero et al² first described the new feature as a central white patch characterized by shiny white streaks. The most frequent dermoscopic pattern associated with dermatofibromas is the central white scarlike patch and peripheral delicate pigment network.^1,4 Arpaia et al⁴ observed that dermoscopic patterns may correspond to distinct sequential stages of the formation of dermatofibroma. The linear character we described may be related to a variant of scarring keloid dermatofibroma.⁵

To the Editor:

Dermatofibroma is a common cutaneous lesion that most frequently affects young or middle-aged adults, especially women.¹ Clinically, it appears as a firm, pink or brown nodule. It may be painful or show a tendency for scarring. The pathognomonic feature of dermatofibroma, regarded as a fibrohistiocytic tumor, is the so-called button sign caused by skin depression following pressure. We present a unique case of elongated dermatofibroma with a linear, white, scarlike patch with a brownish pigmented network and globules.

A 40-year-old woman presented with a linear elongated lesion localized to the right side of the infrascapular region of 10 years’ duration. The lesion initially was a small brownish plaque. There was no history of trauma or scratching. Over the next 10 years, the lesion slowly progressed, finally becoming a linear, atrophic, brownish plaque that was 2.5-cm long (Figure 1). The button sign was positive. On dermoscopy the central, elongated, white patch was visualized not as a typical round patch but as a scarlike white line (Figure 2A) surrounded by a brownish network that was especially pronounced in the distal parts of the lesion. In the upper part of the lesion, multiple marginally disseminated, dark brown dots were present. Brownish globules within the linear white patch also were observed in the lower central part. Figure 2B presents a dermoscopic picture of the linear variant of dermatofibroma. For cosmetic reasons, the patient underwent total surgical excision of the lesion. Histopathology revealed distinct characteristics of dermatofibroma (Figures 3A and 3B).

The most common features of dermatofibromas seen in polarized and nonpolarized dermoscopy are central white scarlike patches, brown globulelike structures, vascular structures, and a peripheral fine pigmented network.² Kilinc Karaarslan et al³ described atypical dermatofibromas with linear irregular crypts, which were seen in 26.9% of all studied cases. These irregular crypts were mainly medium in size (10 lesions), with only 2 lesions being tiny and regularly distributed. Only one lesion had atypical clinical and dermoscopic features occurring as an atrophic plaque with multiple small scarlike areas and peripherally distributed pigment network.³ Based on this typology, we believe our patient represents a case of elongated dermatofibroma that could be an atrophic variant of dermatofibroma. This form would not appear as a small scarlike area with pigment network in a somewhat patchy distribution³ but as a scarlike linear chord with a bipolar pigment network. Zaballos et al¹ described 10 dermoscopic patterns of dermatofibroma (N=412); the most common was a central white patch and peripheral pigment network in approximately 35% of cases. A white scarlike patch was observed in 57.0% of dermat-ofibromas in 4 variants: (1) a solitary structure located in the center; (2) multiple white scarlike patches; (3) white scarlike patch extending throughout the lesion or irregularly distributed; and (4) white network (central, total, or irregular).¹ Agero et al² first described the new feature as a central white patch characterized by shiny white streaks. The most frequent dermoscopic pattern associated with dermatofibromas is the central white scarlike patch and peripheral delicate pigment network.^1,4 Arpaia et al⁴ observed that dermoscopic patterns may correspond to distinct sequential stages of the formation of dermatofibroma. The linear character we described may be related to a variant of scarring keloid dermatofibroma.⁵