Whitney McKnight

NEW ORLEANS – Noninvasive prenatal testing using cell-free fetal DNA found in the maternal bloodstream detects more than 80% of the most common trisomies, including the one for Down syndrome, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Expectant mothers and their treating physicians now may have a wider range of options for balancing the risks inherent in the more invasive kinds of diagnostic testing, such as chorionic villus sampling and amniocentesis, against the desire for such tests’ near-perfect diagnostic accuracy, according to Dr. Mary Norton.

"Some of the other screening tests that we use, some of the ultrasound screens and some blood tests, have a number of false positives," the study’s presenter, Dr. Norton, vice chair of clinical and translational genetics at the University of California, San Francisco, said in an interview.

For the majority of women, the screening tests show no fetal abnormalities, but the experience can unnerve some women, who find that the test just isn’t worth the risk, said Dr. Norton. Current recommendations from the American College of Obstetricians and Gynecologists (ACOG) are that noninvasive prenatal testing (NIPT) only be offered to high-risk pregnant women as an alternative to invasive testing if integrated ultrasound/blood test screens come back positive.

While diagnostic invasive testing offers "near 100% accuracy," there is a 1 in 500 chance the woman will miscarry after having such a procedure, Dr. Norton said. NIPT, which was introduced into clinical practice in 2011, relies on a simple blood test and is typically performed during the second trimester.

"For a woman who is losing sleep with worry that her fetus may have a chromosome problem, having a test like an amniocentesis that comes back normal may allow her to enjoy the rest of her pregnancy," said Dr. Norton. "For someone whose goal is to avoid diagnostic testing at all costs, to avoid the fear of having a false positive, [NIPT] may be better to detect fewer things but to avoid false positives."

Using the California Prenatal Screening Program database from March 2009 through December 2012, Dr. Norton and her colleagues reviewed all karyotype results from invasive diagnostic tests of singleton pregnancies performed after a prenatal screen indicated possible abnormalities. In all, 26,059 results were analyzed and divided according to either the abnormalities that NIPT is currently able to detect, including nonmosaic trisomies 13, 18, and 21 and sex-chromosomal aneuploidy; or abnormalities currently undetectable by NIPT, such as mosaicism.

During the study period, more than 1.3 million women were screened, with just over 5% (68,990) screening positive for trisomy 18 or 21. Of screen-positive women, nearly 38% (26,059) assented to an invasive prenatal test; of these, 12% (2,993) came back with abnormal results. Just more than 83% (2,488) of those abnormalities were ones detectable by NIPT, while just less than 17% (511) were not. The most common abnormal result, at 53% (1,592), was trisomy 21 (Down syndrome), which has been shown to comprise more than half of all abnormalities detected prenatally.

Women aged 35-39 years composed more than a third of all women studied. While in women under age 30, NIPT misses about 22% of aneuploidies, Dr. Norton said in her presentation that in women over age 45, that number drops dramatically to 8%, largely because of the correlative risk for trisomy 18 and 21 and advanced maternal age.

She noted that one of the limitations of the study was the fact that it included only screen-positive women, and thus the study group was "enriched" for trisomy 21; hence, the results cannot be generalized to the unscreened population, which has a different rate and spectrum of fetal abnormalities.

"Our calculations are for potential detection by NIPT for the target disorders. While the sensitivity is high, it is not 100%; therefore, the overall detection for all chromosomal abnormalities will be less than the 83% we report," Dr. Norton told the audience. "In addition, only 38% of screen-positive women chose to have invasive testing, and those declining such testing might have had different risks, and therefore different outcomes."

[email protected]

NEW ORLEANS – Noninvasive prenatal testing using cell-free fetal DNA found in the maternal bloodstream detects more than 80% of the most common trisomies, including the one for Down syndrome, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Expectant mothers and their treating physicians now may have a wider range of options for balancing the risks inherent in the more invasive kinds of diagnostic testing, such as chorionic villus sampling and amniocentesis, against the desire for such tests’ near-perfect diagnostic accuracy, according to Dr. Mary Norton.

"Some of the other screening tests that we use, some of the ultrasound screens and some blood tests, have a number of false positives," the study’s presenter, Dr. Norton, vice chair of clinical and translational genetics at the University of California, San Francisco, said in an interview.

For the majority of women, the screening tests show no fetal abnormalities, but the experience can unnerve some women, who find that the test just isn’t worth the risk, said Dr. Norton. Current recommendations from the American College of Obstetricians and Gynecologists (ACOG) are that noninvasive prenatal testing (NIPT) only be offered to high-risk pregnant women as an alternative to invasive testing if integrated ultrasound/blood test screens come back positive.

While diagnostic invasive testing offers "near 100% accuracy," there is a 1 in 500 chance the woman will miscarry after having such a procedure, Dr. Norton said. NIPT, which was introduced into clinical practice in 2011, relies on a simple blood test and is typically performed during the second trimester.

"For a woman who is losing sleep with worry that her fetus may have a chromosome problem, having a test like an amniocentesis that comes back normal may allow her to enjoy the rest of her pregnancy," said Dr. Norton. "For someone whose goal is to avoid diagnostic testing at all costs, to avoid the fear of having a false positive, [NIPT] may be better to detect fewer things but to avoid false positives."

Using the California Prenatal Screening Program database from March 2009 through December 2012, Dr. Norton and her colleagues reviewed all karyotype results from invasive diagnostic tests of singleton pregnancies performed after a prenatal screen indicated possible abnormalities. In all, 26,059 results were analyzed and divided according to either the abnormalities that NIPT is currently able to detect, including nonmosaic trisomies 13, 18, and 21 and sex-chromosomal aneuploidy; or abnormalities currently undetectable by NIPT, such as mosaicism.

During the study period, more than 1.3 million women were screened, with just over 5% (68,990) screening positive for trisomy 18 or 21. Of screen-positive women, nearly 38% (26,059) assented to an invasive prenatal test; of these, 12% (2,993) came back with abnormal results. Just more than 83% (2,488) of those abnormalities were ones detectable by NIPT, while just less than 17% (511) were not. The most common abnormal result, at 53% (1,592), was trisomy 21 (Down syndrome), which has been shown to comprise more than half of all abnormalities detected prenatally.

Women aged 35-39 years composed more than a third of all women studied. While in women under age 30, NIPT misses about 22% of aneuploidies, Dr. Norton said in her presentation that in women over age 45, that number drops dramatically to 8%, largely because of the correlative risk for trisomy 18 and 21 and advanced maternal age.

She noted that one of the limitations of the study was the fact that it included only screen-positive women, and thus the study group was "enriched" for trisomy 21; hence, the results cannot be generalized to the unscreened population, which has a different rate and spectrum of fetal abnormalities.

"Our calculations are for potential detection by NIPT for the target disorders. While the sensitivity is high, it is not 100%; therefore, the overall detection for all chromosomal abnormalities will be less than the 83% we report," Dr. Norton told the audience. "In addition, only 38% of screen-positive women chose to have invasive testing, and those declining such testing might have had different risks, and therefore different outcomes."

[email protected]

NEW ORLEANS – Noninvasive prenatal testing using cell-free fetal DNA found in the maternal bloodstream detects more than 80% of the most common trisomies, including the one for Down syndrome, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Expectant mothers and their treating physicians now may have a wider range of options for balancing the risks inherent in the more invasive kinds of diagnostic testing, such as chorionic villus sampling and amniocentesis, against the desire for such tests’ near-perfect diagnostic accuracy, according to Dr. Mary Norton.

"Some of the other screening tests that we use, some of the ultrasound screens and some blood tests, have a number of false positives," the study’s presenter, Dr. Norton, vice chair of clinical and translational genetics at the University of California, San Francisco, said in an interview.

For the majority of women, the screening tests show no fetal abnormalities, but the experience can unnerve some women, who find that the test just isn’t worth the risk, said Dr. Norton. Current recommendations from the American College of Obstetricians and Gynecologists (ACOG) are that noninvasive prenatal testing (NIPT) only be offered to high-risk pregnant women as an alternative to invasive testing if integrated ultrasound/blood test screens come back positive.

While diagnostic invasive testing offers "near 100% accuracy," there is a 1 in 500 chance the woman will miscarry after having such a procedure, Dr. Norton said. NIPT, which was introduced into clinical practice in 2011, relies on a simple blood test and is typically performed during the second trimester.

"For a woman who is losing sleep with worry that her fetus may have a chromosome problem, having a test like an amniocentesis that comes back normal may allow her to enjoy the rest of her pregnancy," said Dr. Norton. "For someone whose goal is to avoid diagnostic testing at all costs, to avoid the fear of having a false positive, [NIPT] may be better to detect fewer things but to avoid false positives."

Using the California Prenatal Screening Program database from March 2009 through December 2012, Dr. Norton and her colleagues reviewed all karyotype results from invasive diagnostic tests of singleton pregnancies performed after a prenatal screen indicated possible abnormalities. In all, 26,059 results were analyzed and divided according to either the abnormalities that NIPT is currently able to detect, including nonmosaic trisomies 13, 18, and 21 and sex-chromosomal aneuploidy; or abnormalities currently undetectable by NIPT, such as mosaicism.

During the study period, more than 1.3 million women were screened, with just over 5% (68,990) screening positive for trisomy 18 or 21. Of screen-positive women, nearly 38% (26,059) assented to an invasive prenatal test; of these, 12% (2,993) came back with abnormal results. Just more than 83% (2,488) of those abnormalities were ones detectable by NIPT, while just less than 17% (511) were not. The most common abnormal result, at 53% (1,592), was trisomy 21 (Down syndrome), which has been shown to comprise more than half of all abnormalities detected prenatally.

Women aged 35-39 years composed more than a third of all women studied. While in women under age 30, NIPT misses about 22% of aneuploidies, Dr. Norton said in her presentation that in women over age 45, that number drops dramatically to 8%, largely because of the correlative risk for trisomy 18 and 21 and advanced maternal age.

She noted that one of the limitations of the study was the fact that it included only screen-positive women, and thus the study group was "enriched" for trisomy 21; hence, the results cannot be generalized to the unscreened population, which has a different rate and spectrum of fetal abnormalities.

"Our calculations are for potential detection by NIPT for the target disorders. While the sensitivity is high, it is not 100%; therefore, the overall detection for all chromosomal abnormalities will be less than the 83% we report," Dr. Norton told the audience. "In addition, only 38% of screen-positive women chose to have invasive testing, and those declining such testing might have had different risks, and therefore different outcomes."

[email protected]

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

"It is a hot topic because there is increasing interest in medicine with regard to the microbiome and how our health is affected by it," said Dr. William Grobman, program chair for the Society for Maternal-Fetal Medicine’s annual meeting. "Preterm birth remains poorly understood, but there is intriguing evidence that its occurrence may be related to alterations in the microbiome."

To explore the potential relationship between cervicovaginal microbiota and preterm birth, Dr. Michal Elovitz, director of the maternal and child health research program at the University of Pennsylvania, Philadelphia, led a team in a nested case-control study of 46 women. She presented her results at the meeting.

Dr. Elovitz and her colleagues tested vaginal swabs taken from pregnant women during 20-24 weeks’ gestation, and again during 24-28 weeks. After the women delivered, the cervicovaginal specimens from women who had preterm deliveries were compared with those taken from women who delivered at term.

The researchers tested the DNA from the samples and characterized the microbial communities. Vaginal samples were characterized into community state types (CSTs) based on which bacteria dominated the microbial community. The first group, CST I, is dominated by Lactobacillus crispatus, which according to the Dr. Elovitz is traditionally considered a beneficial bacteria. CST III is dominated by L. iners, and CST IV is dominated by anaerobic bacteria, typical in bacterial vaginosis.

In the 14 women who had a preterm birth, the CST proportions were significantly different than those who delivered at term. In the preterm cohort, 17% had CST I, 61% had CST III, and 22% had CST IV.

In the term cohort, 35% had CST I, 37% had CST III, and 33% had CST IV (P = .012). The percentage of women who had no CST III was higher in women delivering at term than in those who delivered prematurely: 68% vs. 39% (P =.002).

"The percent of non–CST-III was significantly lower in samples from women delivering preterm than term. Notably, the differences in these microbial communities were evident in the late second trimester of pregnancy, weeks if not months prior to the preterm birth," said Dr. Elovitz.

Seventy-eight percent of the women in the study were black; Dr. Elovitz and her colleagues conducted a subanalysis of only those women. "And what we found is that the results were even stronger."

"The implications are very broad, and hopefully very clinically impactful. The microbiome is modifiable. We can find ways to change it," said Dr. Elovitz. The challenge now, she said, is to determine whether the microbiome is just a marker, or if it’s a cause. If microbiota are implicated, "there is a whole new window of opportunity for therapeutics to reduce preterm birth."

Dr. Elovitz did not have any relevant disclosures.

[email protected]

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

"It is a hot topic because there is increasing interest in medicine with regard to the microbiome and how our health is affected by it," said Dr. William Grobman, program chair for the Society for Maternal-Fetal Medicine’s annual meeting. "Preterm birth remains poorly understood, but there is intriguing evidence that its occurrence may be related to alterations in the microbiome."

To explore the potential relationship between cervicovaginal microbiota and preterm birth, Dr. Michal Elovitz, director of the maternal and child health research program at the University of Pennsylvania, Philadelphia, led a team in a nested case-control study of 46 women. She presented her results at the meeting.

Dr. Elovitz and her colleagues tested vaginal swabs taken from pregnant women during 20-24 weeks’ gestation, and again during 24-28 weeks. After the women delivered, the cervicovaginal specimens from women who had preterm deliveries were compared with those taken from women who delivered at term.

The researchers tested the DNA from the samples and characterized the microbial communities. Vaginal samples were characterized into community state types (CSTs) based on which bacteria dominated the microbial community. The first group, CST I, is dominated by Lactobacillus crispatus, which according to the Dr. Elovitz is traditionally considered a beneficial bacteria. CST III is dominated by L. iners, and CST IV is dominated by anaerobic bacteria, typical in bacterial vaginosis.

In the 14 women who had a preterm birth, the CST proportions were significantly different than those who delivered at term. In the preterm cohort, 17% had CST I, 61% had CST III, and 22% had CST IV.

In the term cohort, 35% had CST I, 37% had CST III, and 33% had CST IV (P = .012). The percentage of women who had no CST III was higher in women delivering at term than in those who delivered prematurely: 68% vs. 39% (P =.002).

"The percent of non–CST-III was significantly lower in samples from women delivering preterm than term. Notably, the differences in these microbial communities were evident in the late second trimester of pregnancy, weeks if not months prior to the preterm birth," said Dr. Elovitz.

Seventy-eight percent of the women in the study were black; Dr. Elovitz and her colleagues conducted a subanalysis of only those women. "And what we found is that the results were even stronger."

"The implications are very broad, and hopefully very clinically impactful. The microbiome is modifiable. We can find ways to change it," said Dr. Elovitz. The challenge now, she said, is to determine whether the microbiome is just a marker, or if it’s a cause. If microbiota are implicated, "there is a whole new window of opportunity for therapeutics to reduce preterm birth."

Dr. Elovitz did not have any relevant disclosures.

[email protected]

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

"It is a hot topic because there is increasing interest in medicine with regard to the microbiome and how our health is affected by it," said Dr. William Grobman, program chair for the Society for Maternal-Fetal Medicine’s annual meeting. "Preterm birth remains poorly understood, but there is intriguing evidence that its occurrence may be related to alterations in the microbiome."

To explore the potential relationship between cervicovaginal microbiota and preterm birth, Dr. Michal Elovitz, director of the maternal and child health research program at the University of Pennsylvania, Philadelphia, led a team in a nested case-control study of 46 women. She presented her results at the meeting.

Dr. Elovitz and her colleagues tested vaginal swabs taken from pregnant women during 20-24 weeks’ gestation, and again during 24-28 weeks. After the women delivered, the cervicovaginal specimens from women who had preterm deliveries were compared with those taken from women who delivered at term.

The researchers tested the DNA from the samples and characterized the microbial communities. Vaginal samples were characterized into community state types (CSTs) based on which bacteria dominated the microbial community. The first group, CST I, is dominated by Lactobacillus crispatus, which according to the Dr. Elovitz is traditionally considered a beneficial bacteria. CST III is dominated by L. iners, and CST IV is dominated by anaerobic bacteria, typical in bacterial vaginosis.

In the 14 women who had a preterm birth, the CST proportions were significantly different than those who delivered at term. In the preterm cohort, 17% had CST I, 61% had CST III, and 22% had CST IV.

In the term cohort, 35% had CST I, 37% had CST III, and 33% had CST IV (P = .012). The percentage of women who had no CST III was higher in women delivering at term than in those who delivered prematurely: 68% vs. 39% (P =.002).

"The percent of non–CST-III was significantly lower in samples from women delivering preterm than term. Notably, the differences in these microbial communities were evident in the late second trimester of pregnancy, weeks if not months prior to the preterm birth," said Dr. Elovitz.

Seventy-eight percent of the women in the study were black; Dr. Elovitz and her colleagues conducted a subanalysis of only those women. "And what we found is that the results were even stronger."

"The implications are very broad, and hopefully very clinically impactful. The microbiome is modifiable. We can find ways to change it," said Dr. Elovitz. The challenge now, she said, is to determine whether the microbiome is just a marker, or if it’s a cause. If microbiota are implicated, "there is a whole new window of opportunity for therapeutics to reduce preterm birth."

Dr. Elovitz did not have any relevant disclosures.

[email protected]

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

In a video interview, Dr. Michal Elovitz of the University of Pennsylvania, Philadelphia, discussed a study exploring the role the microbiome plays in high-risk pregnancies and preterm births, and she outlines how better understanding could reshape clinical practice.

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

In a video interview, Dr. Michal Elovitz of the University of Pennsylvania, Philadelphia, discussed a study exploring the role the microbiome plays in high-risk pregnancies and preterm births, and she outlines how better understanding could reshape clinical practice.

NEW ORLEANS – Could the cervicovaginal microbiome be responsible for some preterm births?

In a video interview, Dr. Michal Elovitz of the University of Pennsylvania, Philadelphia, discussed a study exploring the role the microbiome plays in high-risk pregnancies and preterm births, and she outlines how better understanding could reshape clinical practice.

NEW ORLEANS – The rate of cesarean section in the United States has risen dramatically in the past 2 decades, accounting for 30% of all deliveries in 2011.

Several factors are driving the increase, according to the Society for Maternal-Fetal Medicine, which sponsored the annual Pregnancy Meeting. Women are waiting until later in life to have children, and their obesity rates are higher than ever before – both of which increase the risk of medical complications during pregnancy. Fear of malpractice also motivates some ob.gyns. to rely on C-sections.

But the most common reason for a woman to have a C-section is that she has had one before, explained Dr. George Saade, director of the division of maternal-fetal medicine at the University of Texas Medical Branch, Galveston. In a video interview, Dr. Saade discussed what’s fueling the rise, and what physicians must do to reduce C-section rates.

[email protected]

NEW ORLEANS – The rate of cesarean section in the United States has risen dramatically in the past 2 decades, accounting for 30% of all deliveries in 2011.

Several factors are driving the increase, according to the Society for Maternal-Fetal Medicine, which sponsored the annual Pregnancy Meeting. Women are waiting until later in life to have children, and their obesity rates are higher than ever before – both of which increase the risk of medical complications during pregnancy. Fear of malpractice also motivates some ob.gyns. to rely on C-sections.

But the most common reason for a woman to have a C-section is that she has had one before, explained Dr. George Saade, director of the division of maternal-fetal medicine at the University of Texas Medical Branch, Galveston. In a video interview, Dr. Saade discussed what’s fueling the rise, and what physicians must do to reduce C-section rates.

[email protected]

NEW ORLEANS – The rate of cesarean section in the United States has risen dramatically in the past 2 decades, accounting for 30% of all deliveries in 2011.

Several factors are driving the increase, according to the Society for Maternal-Fetal Medicine, which sponsored the annual Pregnancy Meeting. Women are waiting until later in life to have children, and their obesity rates are higher than ever before – both of which increase the risk of medical complications during pregnancy. Fear of malpractice also motivates some ob.gyns. to rely on C-sections.

But the most common reason for a woman to have a C-section is that she has had one before, explained Dr. George Saade, director of the division of maternal-fetal medicine at the University of Texas Medical Branch, Galveston. In a video interview, Dr. Saade discussed what’s fueling the rise, and what physicians must do to reduce C-section rates.

[email protected]

ATLANTA – It’s too soon to disrupt current obesity treatment by declaring food addiction to be a clinical condition, according to Dr. Paul Fletcher.

"If we are to employ [the term] food addiction ... it needs a firm scientific basis," said Dr. Fletcher, who is the Bernard Wolfe Professor of Health Neuroscience in the department of psychiatry at University of Cambridge (England).

Organized medicine took the first step toward recognizing food addiction as a clinical diagnosis with the 2013 inclusion of binge eating disorder (BED) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). That recognition has the potential to set the stage for an overhaul in delivery and funding of obesity treatment as well as how people with pathologic eating behaviors are viewed.

Obesogenic environment

For some, the answer to obesity and food addiction is to remove unhealthful foods from the environment. And to address "powerful environmental drives to consume them," Dr. Hisham Ziauddeen, a Wellcome Trust Fellow in Translational Medicine and Therapeutics at Cambridge, said in an interview.

In a separate presentation at a meeting, sponsored by the Obesity Society and the Society for the Study of Ingestive Behavior, Ashley Gearhardt, Ph.D., noted that researchers do not know whether food addiction exists. "The science is emerging." Foods high in fat and sugar, especially when aggressively marketed to children, are the chief culprits of the obesity epidemic, according to Dr. Gearhardt, a clinical psychologist at the University of Michigan, Ann Arbor.

"If scientific evidence identifies that certain foods are also capable of hijacking the brain in an addictive manner, it would likely be a landmark change that would support bold policy approaches that focus on improving the food environment," she has said (Biol. Psychiatry 2013;73:802-3).

Current research in the field is focused on the individual risk factors for compulsive eating, such as impulsivity or reward sensitivity, Dr. Gearhardt said. However, the lack of addictive behaviors associated with "minimally processed foods that are relatively low in sugar and fat, such as apples or chicken breasts," means research now needs to determine if there is something about the food or behavior "that leads to compulsive problematic use," she said in an interview.

"Individual approaches may be helpful in developing clinical interventions but will touch the lives of far fewer people than will policy changes that affect entire populations," she said.

Dr. Gearhardt and her associates sought to link obesity to addictive patterning in the brain through the combined use of functional neuroimaging (fMRI) and scores on the Yale Food Addiction Scale (YFAS), which applies substance-dependence criteria in the DSM-IV-TR as a type of metric for addictive eating behaviors.

The investigators used fMRI maps of participants’ brain activation when they were given food cues of either a tasteless substance or a chocolate milkshake high in fat and sugar. These images were then compared with the participants’ scores from the YFAS. The group was a mixture of both lean and obese women (Arch. Gen. Psychiatry. 2011;68:808-16).

The researchers found that when presented with a chocolate milkshake, those with higher YFAS scores, regardless of body mass index, experienced "significantly greater activation" in brain regions associated with dopaminergic release, including the anterior cingulate cortex. Those with the highest YFAS scores experienced a significant increase in activity of the dorsolateral prefrontal cortex.

‘Elegant experiments’

While fMRI research into the neurobiologic response to food has "generated some very elegant experiments," according to Dr. Fletcher, he is concerned that food addiction proponents have neglected to see these data in a larger context. "The literature is hugely inconsistent, and ignoring this fact may be inconvenient ... but if we continue to do so, it will come back to slap us in the face."

Because neuroimages "are often ambiguous, unless they are constrained by a specific hypothesis, it becomes more like reading tarot cards than interpreting scientific data," he said. "There is a dangerous tendency for people to have a particular perspective and then, no matter what the fMRI data show, to interpret them according to the perspective with which they started out."

And while this free hand with data interpretation happens generally, Dr. Fletcher said he has been "particularly struck" by its occurrence in the food addiction field. "There seem to be very few constraints on interpretation of the regional activation," he said, noting that whether researchers are looking at obesity, binge-eating, or anyone assumed to have a food addition. "Inevitably, [the researchers] find differences in neural activation in such groups but the interpretations of those activations are often post hoc and heavily biased by what the researchers believed in the first place."

As an example, he cited how activity in the anterior cingulate cortex in overweight people given food cues may be interpreted as a sign of craving. "But this is an unjustified inference because we do not know what the anterior cingulate cortex does and it far more frequently related to other processes than to craving."

Dr. Fletcher and his colleagues’ alarm over this "oversimplification of data" prompted a polite, but impassioned, back and forth with Dr. Gearhardt and her associates, published in Nature Reviews Neuroscience (2012;13:279-86 [doi:10.1038/nrn3212]); (2012;13:514 [doi:10.1038/nrn3212-c1]); (2012;13:514 [doi:10.1038/nrn3212-c2]).

In the first of these editorials, Dr. Fletcher and his coauthors wrote that "the messages now emerging from the neuroscientific research community may therefore have an unprecedented impact on policy development," and in another, urged the adoption of "a more detailed consideration" of how to explore food addiction, particularly since cognitive neuroscience is already moving the field beyond ideas based "purely on clinical overlap" and the model of addiction as delineated in the DSM-IV-TR.

Obesity subsets

"Dr. Fletcher and I agree that the concept of ‘food addiction’ is still an open question," Dr. Gearhardt said in an interview. "My group believes that there is evidence building that suggests it is plausible that an addictive process contributes to problematic eating in some circumstances, especially for eaters who exhibit behavioral phenotypes."

Binge eating, emotional eating, and other pathologies surrounding attitudes toward food also were noted in participants with high YFAS scores in Dr. Gearhardt’s study. "We see evidence of addictive-like processes contributing to problematic eating even for individuals who do not meet the criteria for BED," she said.

Dr. Fletcher noted that "there is a clear degree of clinical overlap between obesity and binge eating, particularly binge eating disorder and drug addiction." Specifically, tolerance, withdrawal, persistent desire for food, eating more than intended, and the diminishment of social engagement in exchange for more time spent acquiring and ingesting food all parallel drug addiction. "However, we don’t know what the overlap is," said Dr. Fletcher. "Is it sugar? Is it fat? Is it a combination? We really don’t know yet."

Populations vs. individuals

"If certain foods are addictive, this may partially explain the difficulty people experience in achieving sustainable weight loss," according to Dr. Gearhardt in commenting on the fMRI study results. "Ubiquitous food advertising and the availability of inexpensive palatable foods may make it extremely difficult to adhere to healthier food choices because the omnipresent food cues trigger the reward system."

Dr. Gearhardt speculated that a focus on specific food ingredients being at the root of addiction-linked obesity may spur activism by manufacturers. "The food industry will likely use any inconsistency in the food addiction literature to plant doubt, attack scientists’ credibility, or fund negative studies," they wrote.

By focusing on how detrimental the food environment has become as a result of "heavily marketed foods that interact with the brain in harmful ways," the public may be more likely to support restrictive policies such as "taxing addictive foods, limiting marketing of these foods to children, and enacting zoning laws that limit the number of vendors selling such foods" among other measures, she wrote.

Dr. Fletcher acknowledged that there is likely a legitimate "battle to be joined" against marketers of junk food and other agents contributing to a deleterious food environment, but attacking the problem at the societal level without consideration of the potential impact on the individual will ultimately backfire. "We must be very careful about how we line up our troops," he said.

"Changing behavior at a population level, which indubitably is required, is not going to be easy," said Dr. Ziauddeen. "As well as the resistance of those with vested interests, such changes will be considered widely unacceptable if they are perceived to entail a loss of liberty."

Although Dr. Fletcher and Dr. Ziauddeen agree a lack of willpower and moral frailty are antiquated notions of why people become obese, assuming that diagnosing people as food addicts will protect them, either from stigmatization or any unforeseen effects of policy changes, is short-sighted.

"Based on our experience with drug addictions over the centuries, it is hard to think that food addiction will not come with some stigma and the consequences thereof," he said.

And Dr. Ziauddeen agreed that, "If the science is shaky and hard to defend, it will be ripped apart." Beyond it possibly being "indefensible" in the face of the opposition from processed food manufacturers, thus setting the field back on its heels, there is the danger of a loss of personal liberty that results, not for the sake of the greater good, but solely from policies based on shoddy science.

"The removal of choice is less threatening if it is done to protect against a situation in which the individual has no real choice anyway, as is the case with addictive substances," said Dr. Ziauddeen. "In short, if there is an addictive agent in some foods, then policy change and legislation can be seen as protective rather than restrictive." This is only possible however, he said, if there is "clear, consistent evidence that there is indeed an addictive substance in food."

And yet, regarding a connection between obesity and food addiction, "the most striking finding is complete inconsistency," said Dr. Fletcher. "I would like to see the same sorts of changes that those supporting food addiction would like, but I do not think that we are going to succeed by using a poorly specified concept with little real evidence to back it up."

Dopamine response not reliable measure

"Food addiction may well exist, [but] even then, it may only explain a tiny fraction of obesity and overeating," according to Dr. Fletcher. "Perhaps the major problem is our general limitations in our often dopaminergically centered views of what constitutes addiction."

A full understanding of the brain’s pathophysiology is still under development, he said. But in addition to classic behavioral manifestations, such as persistent use of a substance, accepted components of addiction include reduced dopamine-receptor density in the ventral striatum and a flip in the neurocircuitry for decision making from the ventral to the dorsal striatum.

Otherwise, he said, conclusive statements about the neurobiology of addiction are suspect. "When we run a functional neuroimaging experiment, we are looking at many different brain regions and, for pretty much all of these, there is a fairly dense ambiguity about what processes they carry out."

In addition, said Dr. Fletcher, although several researchers have tried to replicate one particular study showing that that showed those with severe obesity had reduced raclopride, an indication their dopamine reception was suppressed, the various findings have been inconsistent, thus, said Dr. Fletcher, "there is no proof that there is reduced dopamine in obesity" (Lancet 2001;357:354-7).

As the field of addiction research advances, there will be a shift in the viewpoint that dopamine is the "end all and be all," in part because there will be a deeper understanding of individual variability to different substances that lead to different forms of eating pathologies, he said. "We need to entertain the notion that no single characteristic will define the nature of reward-processing in obesity and that there may be many routes to positive calorie balance."

Longitudinal studies of individual variability to certain foods also could help better determine the impact of certain foods on the brain, he said.

Winners and ‘losers’

"In terms of those who stand to gain from the acceptance of food addiction," said Dr. Fletcher, "At first glance, this would seem to be the people who offer treatments for food addiction and the people who might make some money by suing [processed food] companies."

Yet, for Dr. Gearhardt, if food addiction is proved, and a direct line can be drawn between the food industry’s intentional manipulation of ingredients to profit from this "brain hijacking," Dr. Gearhardt said, "This brings up the question of industry culpability and the ethics of aggressively marketing it to children."

Dr. Gearhardt also believes the possibility of a clinical food addiction diagnosis for those who struggle with pathological eating might "encourage more people ... to receive professional help rather than beat themselves up for not being able to stick to diet after diet on their own."

Conversely, Dr. Ziauddeen noted what while a food addiction diagnosis may offer someone consolation and motivation to seek help, "What if the person is subject to restrictions or treatments based on the diagnosis?" Specifically, he cited ineligibility for bariatric surgery or less clout in the eyes of the court for child custody. "This does not require a stretch of the imagination," he said. "If you have a diagnosis of alcohol dependence, it influences your chances of receiving a liver transplant. If you have a diagnosis of drug or alcohol addiction, it impacts social care decisions made about your children."

Accepting food addiction as real will affect not only those given the diagnosis, but also the so-called "unaffected" public, said Dr. Fletcher. "If food ‘X’ is addictive, to what extent should it be controlled?" He also suggested that health care provision would experience overhaul: "What will be the effect of diverting funding to food addiction treatment from other obesity-related treatments?"

Food addiction "may help us think of novel and hopefully more effective strategies for treating eating-related concerns," said Dr. Gearhardt.

Regardless, Dr. Fletcher warned that because obesity is multifactorial, and includes molecular, metabolic, behavioral, societal and environmental elements, we should not rush to accept "simplistic" answers, or force things to fit where they actually might not. "The thing I think we need to stop right now is this selective citing because we like the narrative."

Dr. Fletcher, Dr. Ziauddeen, and Dr. Gearhardt had no relevant disclosures.

[email protected]

ATLANTA – It’s too soon to disrupt current obesity treatment by declaring food addiction to be a clinical condition, according to Dr. Paul Fletcher.

"If we are to employ [the term] food addiction ... it needs a firm scientific basis," said Dr. Fletcher, who is the Bernard Wolfe Professor of Health Neuroscience in the department of psychiatry at University of Cambridge (England).

Organized medicine took the first step toward recognizing food addiction as a clinical diagnosis with the 2013 inclusion of binge eating disorder (BED) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). That recognition has the potential to set the stage for an overhaul in delivery and funding of obesity treatment as well as how people with pathologic eating behaviors are viewed.

Obesogenic environment

For some, the answer to obesity and food addiction is to remove unhealthful foods from the environment. And to address "powerful environmental drives to consume them," Dr. Hisham Ziauddeen, a Wellcome Trust Fellow in Translational Medicine and Therapeutics at Cambridge, said in an interview.

In a separate presentation at a meeting, sponsored by the Obesity Society and the Society for the Study of Ingestive Behavior, Ashley Gearhardt, Ph.D., noted that researchers do not know whether food addiction exists. "The science is emerging." Foods high in fat and sugar, especially when aggressively marketed to children, are the chief culprits of the obesity epidemic, according to Dr. Gearhardt, a clinical psychologist at the University of Michigan, Ann Arbor.

"If scientific evidence identifies that certain foods are also capable of hijacking the brain in an addictive manner, it would likely be a landmark change that would support bold policy approaches that focus on improving the food environment," she has said (Biol. Psychiatry 2013;73:802-3).

Current research in the field is focused on the individual risk factors for compulsive eating, such as impulsivity or reward sensitivity, Dr. Gearhardt said. However, the lack of addictive behaviors associated with "minimally processed foods that are relatively low in sugar and fat, such as apples or chicken breasts," means research now needs to determine if there is something about the food or behavior "that leads to compulsive problematic use," she said in an interview.

"Individual approaches may be helpful in developing clinical interventions but will touch the lives of far fewer people than will policy changes that affect entire populations," she said.

Dr. Gearhardt and her associates sought to link obesity to addictive patterning in the brain through the combined use of functional neuroimaging (fMRI) and scores on the Yale Food Addiction Scale (YFAS), which applies substance-dependence criteria in the DSM-IV-TR as a type of metric for addictive eating behaviors.

The investigators used fMRI maps of participants’ brain activation when they were given food cues of either a tasteless substance or a chocolate milkshake high in fat and sugar. These images were then compared with the participants’ scores from the YFAS. The group was a mixture of both lean and obese women (Arch. Gen. Psychiatry. 2011;68:808-16).

The researchers found that when presented with a chocolate milkshake, those with higher YFAS scores, regardless of body mass index, experienced "significantly greater activation" in brain regions associated with dopaminergic release, including the anterior cingulate cortex. Those with the highest YFAS scores experienced a significant increase in activity of the dorsolateral prefrontal cortex.

‘Elegant experiments’

While fMRI research into the neurobiologic response to food has "generated some very elegant experiments," according to Dr. Fletcher, he is concerned that food addiction proponents have neglected to see these data in a larger context. "The literature is hugely inconsistent, and ignoring this fact may be inconvenient ... but if we continue to do so, it will come back to slap us in the face."

Because neuroimages "are often ambiguous, unless they are constrained by a specific hypothesis, it becomes more like reading tarot cards than interpreting scientific data," he said. "There is a dangerous tendency for people to have a particular perspective and then, no matter what the fMRI data show, to interpret them according to the perspective with which they started out."

And while this free hand with data interpretation happens generally, Dr. Fletcher said he has been "particularly struck" by its occurrence in the food addiction field. "There seem to be very few constraints on interpretation of the regional activation," he said, noting that whether researchers are looking at obesity, binge-eating, or anyone assumed to have a food addition. "Inevitably, [the researchers] find differences in neural activation in such groups but the interpretations of those activations are often post hoc and heavily biased by what the researchers believed in the first place."

As an example, he cited how activity in the anterior cingulate cortex in overweight people given food cues may be interpreted as a sign of craving. "But this is an unjustified inference because we do not know what the anterior cingulate cortex does and it far more frequently related to other processes than to craving."

Dr. Fletcher and his colleagues’ alarm over this "oversimplification of data" prompted a polite, but impassioned, back and forth with Dr. Gearhardt and her associates, published in Nature Reviews Neuroscience (2012;13:279-86 [doi:10.1038/nrn3212]); (2012;13:514 [doi:10.1038/nrn3212-c1]); (2012;13:514 [doi:10.1038/nrn3212-c2]).

In the first of these editorials, Dr. Fletcher and his coauthors wrote that "the messages now emerging from the neuroscientific research community may therefore have an unprecedented impact on policy development," and in another, urged the adoption of "a more detailed consideration" of how to explore food addiction, particularly since cognitive neuroscience is already moving the field beyond ideas based "purely on clinical overlap" and the model of addiction as delineated in the DSM-IV-TR.

Obesity subsets

"Dr. Fletcher and I agree that the concept of ‘food addiction’ is still an open question," Dr. Gearhardt said in an interview. "My group believes that there is evidence building that suggests it is plausible that an addictive process contributes to problematic eating in some circumstances, especially for eaters who exhibit behavioral phenotypes."

Binge eating, emotional eating, and other pathologies surrounding attitudes toward food also were noted in participants with high YFAS scores in Dr. Gearhardt’s study. "We see evidence of addictive-like processes contributing to problematic eating even for individuals who do not meet the criteria for BED," she said.

Dr. Fletcher noted that "there is a clear degree of clinical overlap between obesity and binge eating, particularly binge eating disorder and drug addiction." Specifically, tolerance, withdrawal, persistent desire for food, eating more than intended, and the diminishment of social engagement in exchange for more time spent acquiring and ingesting food all parallel drug addiction. "However, we don’t know what the overlap is," said Dr. Fletcher. "Is it sugar? Is it fat? Is it a combination? We really don’t know yet."

Populations vs. individuals

"If certain foods are addictive, this may partially explain the difficulty people experience in achieving sustainable weight loss," according to Dr. Gearhardt in commenting on the fMRI study results. "Ubiquitous food advertising and the availability of inexpensive palatable foods may make it extremely difficult to adhere to healthier food choices because the omnipresent food cues trigger the reward system."

Dr. Gearhardt speculated that a focus on specific food ingredients being at the root of addiction-linked obesity may spur activism by manufacturers. "The food industry will likely use any inconsistency in the food addiction literature to plant doubt, attack scientists’ credibility, or fund negative studies," they wrote.

By focusing on how detrimental the food environment has become as a result of "heavily marketed foods that interact with the brain in harmful ways," the public may be more likely to support restrictive policies such as "taxing addictive foods, limiting marketing of these foods to children, and enacting zoning laws that limit the number of vendors selling such foods" among other measures, she wrote.

Dr. Fletcher acknowledged that there is likely a legitimate "battle to be joined" against marketers of junk food and other agents contributing to a deleterious food environment, but attacking the problem at the societal level without consideration of the potential impact on the individual will ultimately backfire. "We must be very careful about how we line up our troops," he said.

"Changing behavior at a population level, which indubitably is required, is not going to be easy," said Dr. Ziauddeen. "As well as the resistance of those with vested interests, such changes will be considered widely unacceptable if they are perceived to entail a loss of liberty."

Although Dr. Fletcher and Dr. Ziauddeen agree a lack of willpower and moral frailty are antiquated notions of why people become obese, assuming that diagnosing people as food addicts will protect them, either from stigmatization or any unforeseen effects of policy changes, is short-sighted.

"Based on our experience with drug addictions over the centuries, it is hard to think that food addiction will not come with some stigma and the consequences thereof," he said.

And Dr. Ziauddeen agreed that, "If the science is shaky and hard to defend, it will be ripped apart." Beyond it possibly being "indefensible" in the face of the opposition from processed food manufacturers, thus setting the field back on its heels, there is the danger of a loss of personal liberty that results, not for the sake of the greater good, but solely from policies based on shoddy science.

"The removal of choice is less threatening if it is done to protect against a situation in which the individual has no real choice anyway, as is the case with addictive substances," said Dr. Ziauddeen. "In short, if there is an addictive agent in some foods, then policy change and legislation can be seen as protective rather than restrictive." This is only possible however, he said, if there is "clear, consistent evidence that there is indeed an addictive substance in food."

And yet, regarding a connection between obesity and food addiction, "the most striking finding is complete inconsistency," said Dr. Fletcher. "I would like to see the same sorts of changes that those supporting food addiction would like, but I do not think that we are going to succeed by using a poorly specified concept with little real evidence to back it up."

Dopamine response not reliable measure

"Food addiction may well exist, [but] even then, it may only explain a tiny fraction of obesity and overeating," according to Dr. Fletcher. "Perhaps the major problem is our general limitations in our often dopaminergically centered views of what constitutes addiction."

A full understanding of the brain’s pathophysiology is still under development, he said. But in addition to classic behavioral manifestations, such as persistent use of a substance, accepted components of addiction include reduced dopamine-receptor density in the ventral striatum and a flip in the neurocircuitry for decision making from the ventral to the dorsal striatum.

Otherwise, he said, conclusive statements about the neurobiology of addiction are suspect. "When we run a functional neuroimaging experiment, we are looking at many different brain regions and, for pretty much all of these, there is a fairly dense ambiguity about what processes they carry out."

In addition, said Dr. Fletcher, although several researchers have tried to replicate one particular study showing that that showed those with severe obesity had reduced raclopride, an indication their dopamine reception was suppressed, the various findings have been inconsistent, thus, said Dr. Fletcher, "there is no proof that there is reduced dopamine in obesity" (Lancet 2001;357:354-7).

As the field of addiction research advances, there will be a shift in the viewpoint that dopamine is the "end all and be all," in part because there will be a deeper understanding of individual variability to different substances that lead to different forms of eating pathologies, he said. "We need to entertain the notion that no single characteristic will define the nature of reward-processing in obesity and that there may be many routes to positive calorie balance."

Longitudinal studies of individual variability to certain foods also could help better determine the impact of certain foods on the brain, he said.

Winners and ‘losers’

"In terms of those who stand to gain from the acceptance of food addiction," said Dr. Fletcher, "At first glance, this would seem to be the people who offer treatments for food addiction and the people who might make some money by suing [processed food] companies."

Yet, for Dr. Gearhardt, if food addiction is proved, and a direct line can be drawn between the food industry’s intentional manipulation of ingredients to profit from this "brain hijacking," Dr. Gearhardt said, "This brings up the question of industry culpability and the ethics of aggressively marketing it to children."

Dr. Gearhardt also believes the possibility of a clinical food addiction diagnosis for those who struggle with pathological eating might "encourage more people ... to receive professional help rather than beat themselves up for not being able to stick to diet after diet on their own."

Conversely, Dr. Ziauddeen noted what while a food addiction diagnosis may offer someone consolation and motivation to seek help, "What if the person is subject to restrictions or treatments based on the diagnosis?" Specifically, he cited ineligibility for bariatric surgery or less clout in the eyes of the court for child custody. "This does not require a stretch of the imagination," he said. "If you have a diagnosis of alcohol dependence, it influences your chances of receiving a liver transplant. If you have a diagnosis of drug or alcohol addiction, it impacts social care decisions made about your children."

Accepting food addiction as real will affect not only those given the diagnosis, but also the so-called "unaffected" public, said Dr. Fletcher. "If food ‘X’ is addictive, to what extent should it be controlled?" He also suggested that health care provision would experience overhaul: "What will be the effect of diverting funding to food addiction treatment from other obesity-related treatments?"

Food addiction "may help us think of novel and hopefully more effective strategies for treating eating-related concerns," said Dr. Gearhardt.

Regardless, Dr. Fletcher warned that because obesity is multifactorial, and includes molecular, metabolic, behavioral, societal and environmental elements, we should not rush to accept "simplistic" answers, or force things to fit where they actually might not. "The thing I think we need to stop right now is this selective citing because we like the narrative."

Dr. Fletcher, Dr. Ziauddeen, and Dr. Gearhardt had no relevant disclosures.

[email protected]

ATLANTA – It’s too soon to disrupt current obesity treatment by declaring food addiction to be a clinical condition, according to Dr. Paul Fletcher.

"If we are to employ [the term] food addiction ... it needs a firm scientific basis," said Dr. Fletcher, who is the Bernard Wolfe Professor of Health Neuroscience in the department of psychiatry at University of Cambridge (England).

Organized medicine took the first step toward recognizing food addiction as a clinical diagnosis with the 2013 inclusion of binge eating disorder (BED) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). That recognition has the potential to set the stage for an overhaul in delivery and funding of obesity treatment as well as how people with pathologic eating behaviors are viewed.

Obesogenic environment

For some, the answer to obesity and food addiction is to remove unhealthful foods from the environment. And to address "powerful environmental drives to consume them," Dr. Hisham Ziauddeen, a Wellcome Trust Fellow in Translational Medicine and Therapeutics at Cambridge, said in an interview.

In a separate presentation at a meeting, sponsored by the Obesity Society and the Society for the Study of Ingestive Behavior, Ashley Gearhardt, Ph.D., noted that researchers do not know whether food addiction exists. "The science is emerging." Foods high in fat and sugar, especially when aggressively marketed to children, are the chief culprits of the obesity epidemic, according to Dr. Gearhardt, a clinical psychologist at the University of Michigan, Ann Arbor.

"If scientific evidence identifies that certain foods are also capable of hijacking the brain in an addictive manner, it would likely be a landmark change that would support bold policy approaches that focus on improving the food environment," she has said (Biol. Psychiatry 2013;73:802-3).

Current research in the field is focused on the individual risk factors for compulsive eating, such as impulsivity or reward sensitivity, Dr. Gearhardt said. However, the lack of addictive behaviors associated with "minimally processed foods that are relatively low in sugar and fat, such as apples or chicken breasts," means research now needs to determine if there is something about the food or behavior "that leads to compulsive problematic use," she said in an interview.

"Individual approaches may be helpful in developing clinical interventions but will touch the lives of far fewer people than will policy changes that affect entire populations," she said.

Dr. Gearhardt and her associates sought to link obesity to addictive patterning in the brain through the combined use of functional neuroimaging (fMRI) and scores on the Yale Food Addiction Scale (YFAS), which applies substance-dependence criteria in the DSM-IV-TR as a type of metric for addictive eating behaviors.

The investigators used fMRI maps of participants’ brain activation when they were given food cues of either a tasteless substance or a chocolate milkshake high in fat and sugar. These images were then compared with the participants’ scores from the YFAS. The group was a mixture of both lean and obese women (Arch. Gen. Psychiatry. 2011;68:808-16).

The researchers found that when presented with a chocolate milkshake, those with higher YFAS scores, regardless of body mass index, experienced "significantly greater activation" in brain regions associated with dopaminergic release, including the anterior cingulate cortex. Those with the highest YFAS scores experienced a significant increase in activity of the dorsolateral prefrontal cortex.

‘Elegant experiments’

While fMRI research into the neurobiologic response to food has "generated some very elegant experiments," according to Dr. Fletcher, he is concerned that food addiction proponents have neglected to see these data in a larger context. "The literature is hugely inconsistent, and ignoring this fact may be inconvenient ... but if we continue to do so, it will come back to slap us in the face."

Because neuroimages "are often ambiguous, unless they are constrained by a specific hypothesis, it becomes more like reading tarot cards than interpreting scientific data," he said. "There is a dangerous tendency for people to have a particular perspective and then, no matter what the fMRI data show, to interpret them according to the perspective with which they started out."

And while this free hand with data interpretation happens generally, Dr. Fletcher said he has been "particularly struck" by its occurrence in the food addiction field. "There seem to be very few constraints on interpretation of the regional activation," he said, noting that whether researchers are looking at obesity, binge-eating, or anyone assumed to have a food addition. "Inevitably, [the researchers] find differences in neural activation in such groups but the interpretations of those activations are often post hoc and heavily biased by what the researchers believed in the first place."

As an example, he cited how activity in the anterior cingulate cortex in overweight people given food cues may be interpreted as a sign of craving. "But this is an unjustified inference because we do not know what the anterior cingulate cortex does and it far more frequently related to other processes than to craving."

Dr. Fletcher and his colleagues’ alarm over this "oversimplification of data" prompted a polite, but impassioned, back and forth with Dr. Gearhardt and her associates, published in Nature Reviews Neuroscience (2012;13:279-86 [doi:10.1038/nrn3212]); (2012;13:514 [doi:10.1038/nrn3212-c1]); (2012;13:514 [doi:10.1038/nrn3212-c2]).

In the first of these editorials, Dr. Fletcher and his coauthors wrote that "the messages now emerging from the neuroscientific research community may therefore have an unprecedented impact on policy development," and in another, urged the adoption of "a more detailed consideration" of how to explore food addiction, particularly since cognitive neuroscience is already moving the field beyond ideas based "purely on clinical overlap" and the model of addiction as delineated in the DSM-IV-TR.

Obesity subsets

"Dr. Fletcher and I agree that the concept of ‘food addiction’ is still an open question," Dr. Gearhardt said in an interview. "My group believes that there is evidence building that suggests it is plausible that an addictive process contributes to problematic eating in some circumstances, especially for eaters who exhibit behavioral phenotypes."

Binge eating, emotional eating, and other pathologies surrounding attitudes toward food also were noted in participants with high YFAS scores in Dr. Gearhardt’s study. "We see evidence of addictive-like processes contributing to problematic eating even for individuals who do not meet the criteria for BED," she said.

Dr. Fletcher noted that "there is a clear degree of clinical overlap between obesity and binge eating, particularly binge eating disorder and drug addiction." Specifically, tolerance, withdrawal, persistent desire for food, eating more than intended, and the diminishment of social engagement in exchange for more time spent acquiring and ingesting food all parallel drug addiction. "However, we don’t know what the overlap is," said Dr. Fletcher. "Is it sugar? Is it fat? Is it a combination? We really don’t know yet."

Populations vs. individuals

"If certain foods are addictive, this may partially explain the difficulty people experience in achieving sustainable weight loss," according to Dr. Gearhardt in commenting on the fMRI study results. "Ubiquitous food advertising and the availability of inexpensive palatable foods may make it extremely difficult to adhere to healthier food choices because the omnipresent food cues trigger the reward system."

Dr. Gearhardt speculated that a focus on specific food ingredients being at the root of addiction-linked obesity may spur activism by manufacturers. "The food industry will likely use any inconsistency in the food addiction literature to plant doubt, attack scientists’ credibility, or fund negative studies," they wrote.

By focusing on how detrimental the food environment has become as a result of "heavily marketed foods that interact with the brain in harmful ways," the public may be more likely to support restrictive policies such as "taxing addictive foods, limiting marketing of these foods to children, and enacting zoning laws that limit the number of vendors selling such foods" among other measures, she wrote.

Dr. Fletcher acknowledged that there is likely a legitimate "battle to be joined" against marketers of junk food and other agents contributing to a deleterious food environment, but attacking the problem at the societal level without consideration of the potential impact on the individual will ultimately backfire. "We must be very careful about how we line up our troops," he said.

"Changing behavior at a population level, which indubitably is required, is not going to be easy," said Dr. Ziauddeen. "As well as the resistance of those with vested interests, such changes will be considered widely unacceptable if they are perceived to entail a loss of liberty."

Although Dr. Fletcher and Dr. Ziauddeen agree a lack of willpower and moral frailty are antiquated notions of why people become obese, assuming that diagnosing people as food addicts will protect them, either from stigmatization or any unforeseen effects of policy changes, is short-sighted.

"Based on our experience with drug addictions over the centuries, it is hard to think that food addiction will not come with some stigma and the consequences thereof," he said.

And Dr. Ziauddeen agreed that, "If the science is shaky and hard to defend, it will be ripped apart." Beyond it possibly being "indefensible" in the face of the opposition from processed food manufacturers, thus setting the field back on its heels, there is the danger of a loss of personal liberty that results, not for the sake of the greater good, but solely from policies based on shoddy science.

"The removal of choice is less threatening if it is done to protect against a situation in which the individual has no real choice anyway, as is the case with addictive substances," said Dr. Ziauddeen. "In short, if there is an addictive agent in some foods, then policy change and legislation can be seen as protective rather than restrictive." This is only possible however, he said, if there is "clear, consistent evidence that there is indeed an addictive substance in food."

And yet, regarding a connection between obesity and food addiction, "the most striking finding is complete inconsistency," said Dr. Fletcher. "I would like to see the same sorts of changes that those supporting food addiction would like, but I do not think that we are going to succeed by using a poorly specified concept with little real evidence to back it up."

Dopamine response not reliable measure

"Food addiction may well exist, [but] even then, it may only explain a tiny fraction of obesity and overeating," according to Dr. Fletcher. "Perhaps the major problem is our general limitations in our often dopaminergically centered views of what constitutes addiction."

A full understanding of the brain’s pathophysiology is still under development, he said. But in addition to classic behavioral manifestations, such as persistent use of a substance, accepted components of addiction include reduced dopamine-receptor density in the ventral striatum and a flip in the neurocircuitry for decision making from the ventral to the dorsal striatum.

Otherwise, he said, conclusive statements about the neurobiology of addiction are suspect. "When we run a functional neuroimaging experiment, we are looking at many different brain regions and, for pretty much all of these, there is a fairly dense ambiguity about what processes they carry out."

In addition, said Dr. Fletcher, although several researchers have tried to replicate one particular study showing that that showed those with severe obesity had reduced raclopride, an indication their dopamine reception was suppressed, the various findings have been inconsistent, thus, said Dr. Fletcher, "there is no proof that there is reduced dopamine in obesity" (Lancet 2001;357:354-7).

As the field of addiction research advances, there will be a shift in the viewpoint that dopamine is the "end all and be all," in part because there will be a deeper understanding of individual variability to different substances that lead to different forms of eating pathologies, he said. "We need to entertain the notion that no single characteristic will define the nature of reward-processing in obesity and that there may be many routes to positive calorie balance."

Longitudinal studies of individual variability to certain foods also could help better determine the impact of certain foods on the brain, he said.

Winners and ‘losers’

"In terms of those who stand to gain from the acceptance of food addiction," said Dr. Fletcher, "At first glance, this would seem to be the people who offer treatments for food addiction and the people who might make some money by suing [processed food] companies."

Yet, for Dr. Gearhardt, if food addiction is proved, and a direct line can be drawn between the food industry’s intentional manipulation of ingredients to profit from this "brain hijacking," Dr. Gearhardt said, "This brings up the question of industry culpability and the ethics of aggressively marketing it to children."

Dr. Gearhardt also believes the possibility of a clinical food addiction diagnosis for those who struggle with pathological eating might "encourage more people ... to receive professional help rather than beat themselves up for not being able to stick to diet after diet on their own."

Conversely, Dr. Ziauddeen noted what while a food addiction diagnosis may offer someone consolation and motivation to seek help, "What if the person is subject to restrictions or treatments based on the diagnosis?" Specifically, he cited ineligibility for bariatric surgery or less clout in the eyes of the court for child custody. "This does not require a stretch of the imagination," he said. "If you have a diagnosis of alcohol dependence, it influences your chances of receiving a liver transplant. If you have a diagnosis of drug or alcohol addiction, it impacts social care decisions made about your children."

Accepting food addiction as real will affect not only those given the diagnosis, but also the so-called "unaffected" public, said Dr. Fletcher. "If food ‘X’ is addictive, to what extent should it be controlled?" He also suggested that health care provision would experience overhaul: "What will be the effect of diverting funding to food addiction treatment from other obesity-related treatments?"

Food addiction "may help us think of novel and hopefully more effective strategies for treating eating-related concerns," said Dr. Gearhardt.

Regardless, Dr. Fletcher warned that because obesity is multifactorial, and includes molecular, metabolic, behavioral, societal and environmental elements, we should not rush to accept "simplistic" answers, or force things to fit where they actually might not. "The thing I think we need to stop right now is this selective citing because we like the narrative."

Dr. Fletcher, Dr. Ziauddeen, and Dr. Gearhardt had no relevant disclosures.

[email protected]

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

[email protected]

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

[email protected]

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

[email protected]

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

[email protected]

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

[email protected]

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

[email protected]

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

[email protected]

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

[email protected]

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

[email protected]

WASHINGTON - Cardiac and vascular surgery patients are at higher risk for deep vein thrombosis than are general surgery patients, according to data presented at the annual clinical congress of the American College of Surgeons.

In a retrospective analysis of 2,669,772 patients with a median age of 64 years, 43% of whom were males, in the ACS-National Surgical Quality Improvement Program (NSQIP) during 2005-2009, Dr. Faisal Aziz of Penn State Hershey (Pa.) Heart and Vascular Institute and his colleagues sought to determine the actual rate of deep vein thrombosis (DVT) during revascularization procedures, compared with general surgery.

The researchers sorted patients according to DVT risk factors such as age, gender, body mass index over 40 kg/m², and whether the surgery was acute. They then assessed intraoperative factors such as total time to completion and the American Society of Anesthesiology score. They then considered the postoperative factors associated with DVT, such as blood transfusions, return to the operating room, deep wound infection, cardiac arrest, and mortality.

There were 18,512 incidences of DVT, equaling 0.69% of all patients studied. Of those, 0.66% occurred during general surgery, 2.08% occurred during cardiac surgery, and 1% occurred during vascular surgery.

"The implications of our study are that, contrary to popular belief, the incidence of postop DVT is actually higher after cardiac surgery and vascular surgery procedures," he said.

The cardiac surgery procedures associated with the highest DVT incidence rate were tricuspid valve replacement (8%), thoracic endovascular aortic repair (5%), thoracic aortic graft replacement (4%), and pericardial window (4%).

In a comparison of cardiac procedures, tricuspid valve replacement vs. aortic valve replacement had a risk ratio of 3.5 (P < .001). In tricuspid valve replacement vs. coronary artery bypass, the former had a risk ratio of 11.24 (P < .001).

Vascular surgeries with the highest DVT incidence rates were peripheral bypass (1%), amputation (trans-metatarsal, 0.75%; below knee, 1%; above the knee, 1%), and ruptured aortic aneurysms (3.5%).

Comparatively, in ruptured endovascular aneurysm repair (EVAR) vs. elective EVAR, the risk ratio was 3.55 (P < .001). In abdominal aortic aneurysm (AAA) repair, ruptured vs. elective surgeries had a risk ratio of 2.37 (P < .001).

Compared with 80% of general surgery patients, 74% of cardiac surgery patients were 70 years or older (relative risk, 1.12; P = .13); 86% of vascular surgery patients were 70 years or older (RR, 1.1; P < .05).

Male gender was an associated risk factor in 49% of general surgery patients, compared with 70% for cardiac patients (RR, 1.4; P < .001) and 51% for vascular patients (RR, 1.1; P < .001).

Intra- and postoperative factors associated with DVT risk included operation times exceeding 240 minutes and previous DVT. Compared with 21% of general surgery patients, operation time was implicated in 59% of cardiac surgery patients (relative risk, 2.72; P < .001) and 25% of vascular surgery patients (RR, 1.14; P <.001). Blood transfusions affected 13% of cardiac surgery patients (RR, 2.3; P < .001), 6% of vascular surgery patients (RR, 1.3; P < .001), and 6% of general surgery patients.

Compared with 24% for general surgery patients, returning to the operating room was implicated in 27% of cardiac patients (RR, 1.4; P = .27) and 32% of vascular surgery patients (RR, 1.3; P < .001).

"Procedures and perioperative factors associated with high risk of postoperative DVT should be identified, and adequate DVT prophylaxis should be ensured for these patients," Dr. Aziz concluded.

He had no disclosures.

[email protected]

WASHINGTON - Cardiac and vascular surgery patients are at higher risk for deep vein thrombosis than are general surgery patients, according to data presented at the annual clinical congress of the American College of Surgeons.

In a retrospective analysis of 2,669,772 patients with a median age of 64 years, 43% of whom were males, in the ACS-National Surgical Quality Improvement Program (NSQIP) during 2005-2009, Dr. Faisal Aziz of Penn State Hershey (Pa.) Heart and Vascular Institute and his colleagues sought to determine the actual rate of deep vein thrombosis (DVT) during revascularization procedures, compared with general surgery.

The researchers sorted patients according to DVT risk factors such as age, gender, body mass index over 40 kg/m², and whether the surgery was acute. They then assessed intraoperative factors such as total time to completion and the American Society of Anesthesiology score. They then considered the postoperative factors associated with DVT, such as blood transfusions, return to the operating room, deep wound infection, cardiac arrest, and mortality.

There were 18,512 incidences of DVT, equaling 0.69% of all patients studied. Of those, 0.66% occurred during general surgery, 2.08% occurred during cardiac surgery, and 1% occurred during vascular surgery.

"The implications of our study are that, contrary to popular belief, the incidence of postop DVT is actually higher after cardiac surgery and vascular surgery procedures," he said.

The cardiac surgery procedures associated with the highest DVT incidence rate were tricuspid valve replacement (8%), thoracic endovascular aortic repair (5%), thoracic aortic graft replacement (4%), and pericardial window (4%).

In a comparison of cardiac procedures, tricuspid valve replacement vs. aortic valve replacement had a risk ratio of 3.5 (P < .001). In tricuspid valve replacement vs. coronary artery bypass, the former had a risk ratio of 11.24 (P < .001).

Vascular surgeries with the highest DVT incidence rates were peripheral bypass (1%), amputation (trans-metatarsal, 0.75%; below knee, 1%; above the knee, 1%), and ruptured aortic aneurysms (3.5%).

Comparatively, in ruptured endovascular aneurysm repair (EVAR) vs. elective EVAR, the risk ratio was 3.55 (P < .001). In abdominal aortic aneurysm (AAA) repair, ruptured vs. elective surgeries had a risk ratio of 2.37 (P < .001).

Compared with 80% of general surgery patients, 74% of cardiac surgery patients were 70 years or older (relative risk, 1.12; P = .13); 86% of vascular surgery patients were 70 years or older (RR, 1.1; P < .05).

Male gender was an associated risk factor in 49% of general surgery patients, compared with 70% for cardiac patients (RR, 1.4; P < .001) and 51% for vascular patients (RR, 1.1; P < .001).

Intra- and postoperative factors associated with DVT risk included operation times exceeding 240 minutes and previous DVT. Compared with 21% of general surgery patients, operation time was implicated in 59% of cardiac surgery patients (relative risk, 2.72; P < .001) and 25% of vascular surgery patients (RR, 1.14; P <.001). Blood transfusions affected 13% of cardiac surgery patients (RR, 2.3; P < .001), 6% of vascular surgery patients (RR, 1.3; P < .001), and 6% of general surgery patients.

Compared with 24% for general surgery patients, returning to the operating room was implicated in 27% of cardiac patients (RR, 1.4; P = .27) and 32% of vascular surgery patients (RR, 1.3; P < .001).

"Procedures and perioperative factors associated with high risk of postoperative DVT should be identified, and adequate DVT prophylaxis should be ensured for these patients," Dr. Aziz concluded.

He had no disclosures.

[email protected]

WASHINGTON - Cardiac and vascular surgery patients are at higher risk for deep vein thrombosis than are general surgery patients, according to data presented at the annual clinical congress of the American College of Surgeons.

In a retrospective analysis of 2,669,772 patients with a median age of 64 years, 43% of whom were males, in the ACS-National Surgical Quality Improvement Program (NSQIP) during 2005-2009, Dr. Faisal Aziz of Penn State Hershey (Pa.) Heart and Vascular Institute and his colleagues sought to determine the actual rate of deep vein thrombosis (DVT) during revascularization procedures, compared with general surgery.

The researchers sorted patients according to DVT risk factors such as age, gender, body mass index over 40 kg/m², and whether the surgery was acute. They then assessed intraoperative factors such as total time to completion and the American Society of Anesthesiology score. They then considered the postoperative factors associated with DVT, such as blood transfusions, return to the operating room, deep wound infection, cardiac arrest, and mortality.

There were 18,512 incidences of DVT, equaling 0.69% of all patients studied. Of those, 0.66% occurred during general surgery, 2.08% occurred during cardiac surgery, and 1% occurred during vascular surgery.

"The implications of our study are that, contrary to popular belief, the incidence of postop DVT is actually higher after cardiac surgery and vascular surgery procedures," he said.

The cardiac surgery procedures associated with the highest DVT incidence rate were tricuspid valve replacement (8%), thoracic endovascular aortic repair (5%), thoracic aortic graft replacement (4%), and pericardial window (4%).

In a comparison of cardiac procedures, tricuspid valve replacement vs. aortic valve replacement had a risk ratio of 3.5 (P < .001). In tricuspid valve replacement vs. coronary artery bypass, the former had a risk ratio of 11.24 (P < .001).

Vascular surgeries with the highest DVT incidence rates were peripheral bypass (1%), amputation (trans-metatarsal, 0.75%; below knee, 1%; above the knee, 1%), and ruptured aortic aneurysms (3.5%).

Comparatively, in ruptured endovascular aneurysm repair (EVAR) vs. elective EVAR, the risk ratio was 3.55 (P < .001). In abdominal aortic aneurysm (AAA) repair, ruptured vs. elective surgeries had a risk ratio of 2.37 (P < .001).

Compared with 80% of general surgery patients, 74% of cardiac surgery patients were 70 years or older (relative risk, 1.12; P = .13); 86% of vascular surgery patients were 70 years or older (RR, 1.1; P < .05).

Male gender was an associated risk factor in 49% of general surgery patients, compared with 70% for cardiac patients (RR, 1.4; P < .001) and 51% for vascular patients (RR, 1.1; P < .001).

Intra- and postoperative factors associated with DVT risk included operation times exceeding 240 minutes and previous DVT. Compared with 21% of general surgery patients, operation time was implicated in 59% of cardiac surgery patients (relative risk, 2.72; P < .001) and 25% of vascular surgery patients (RR, 1.14; P <.001). Blood transfusions affected 13% of cardiac surgery patients (RR, 2.3; P < .001), 6% of vascular surgery patients (RR, 1.3; P < .001), and 6% of general surgery patients.

Compared with 24% for general surgery patients, returning to the operating room was implicated in 27% of cardiac patients (RR, 1.4; P = .27) and 32% of vascular surgery patients (RR, 1.3; P < .001).

"Procedures and perioperative factors associated with high risk of postoperative DVT should be identified, and adequate DVT prophylaxis should be ensured for these patients," Dr. Aziz concluded.

He had no disclosures.

[email protected]

Improving hospital worker safety will result in improved patient safety, according to the Occupational Safety and Health Administration, which has unveiled a hospital worker safety online resource center.

Worker Safety in Hospitals: Caring for our Caregivers, OSHA's new website aimed at curbing hospital worker injury rates, was introduced during a media teleconference Jan. 16. According to OSHA, injuries occur at a rate of 158 times per 10,000 workers, making hospitals more hazardous work environments than either construction or manufacturing sites.

National workers’ compensation losses from hospital workers total $2 billion annually, said OSHA assistant secretary Dr. David Michaels.

Musculoskeletal injuries, primarily from lifting and shifting patients, are the single biggest worker injury in hospitals, he said. According to OSHA, 16,680 hospital workers missed work because of a musculoskeletal injury sustained while handling a patient.

"Other hazards facing hospital workers include workplace violence, slips and falls, exposure to chemicals including hazardous drugs, exposure to infectious diseases, and needle sticks," said Dr. Michaels.

As part of a joint effort to promote the website, also on the conference call were Dr. John Howard, director of the National Institute for Occupational Safety and Health, and Dr. Erin DuPree, chief medical officer and vice president of the Joint Commission Center for Transforming Healthcare, and Dr. Lucian Leape, chairman of the Lucian Leape Institute at the National Patient Safety Foundation.

The OSHA website offers educational materials on avoiding injury when handling patients, as well as on workplace safety needs and the implementation of safety and health management systems.

The materials were culled from best practices employed at hospitals around the country deemed by OSHA to be "high-reliability organizations," and include tips such as having a daily "safety huddle" that includes a discussion of "great catches" and "near misses" that occurred during daily operations.

"One of the major barriers in making progress in patient safety is that when people report that they’ve made a mistake, they often get punished for it," said Dr. Leape. "What we’ve been trying to get people to understand is that mistakes happen because of bad systems, not bad people. You have to create an environment where you really believe that, and make it safe for people to talk about their errors so you can understand what you need to fix."

Dr. DuPree said the OSHA resources align with Joint Commission requirements such as those for hospitals to have a written plan for managing environmental safety for patients and all persons in hospitals. The Joint Commission expects that all individuals who work in the hospital should not fear retribution for speaking up about their safety concerns, Dr. DuPree said. "Leaders need to value and empower their workers. They need to understand that fear of reprisal and failure to share knowledge can compromise an organization’s ability to improve safety for all," he said.

As part of its efforts to advise hospital administrators on how to create safer work environments for their employees, the U.S. Department of Labor Occupational Safety and Health Administration has created a list of attributes of what it calls "high-reliability organizations."

Self-assessment tools, tip sheets, and other materials intended to help hospitals become high-reliability organizations (HROs) are available at OSHA's new website, Worker Safety in Hospitals: Caring for our Caregivers.

"The heart of these new materials are real life lessons from high-performing hospitals [that] have implemented best practices to reduce workplace injuries while also improving patient safety," said OSHA assistant secretary Dr. David Michaels in a press briefing.

The website emphasizes principles endorsed by the Joint Commission, particularly the promotion of a "no-blame" culture to destigmatize safety interventions. Operational strategies derived from the distillation of these best practices and endorsed by OSHA include the following:

• Sensitivity to operations. That means hospital workers should know what the standard procedures are, and follow them.

• Reluctance to simplify. This tenet calls upon hospital administrators to explore the larger context in which safety failures occur.

• Preoccupation with failure. OSHA warns administrators to "never let success breed complacency" and impels hospital leaders to "focus unceasingly on ways the system can fail" and to encourage staff to "listen to their ‘inner voice’ of concern."

• Deference to expertise. Pulling rank rather than going to the one who has the most direct experience in a situation is discouraged by OSHA.

• Resilience. Basically, know there will be failures, but hopefully only small ones; learn from them and rebound.

Dr. Michaels, Dr. Howard, Dr. DuPree, and Dr. Leape did not report any relevant financial disclosures.

[email protected]

*This article has been updated 1/16/2014.

Improving hospital worker safety will result in improved patient safety, according to the Occupational Safety and Health Administration, which has unveiled a hospital worker safety online resource center.

Worker Safety in Hospitals: Caring for our Caregivers, OSHA's new website aimed at curbing hospital worker injury rates, was introduced during a media teleconference Jan. 16. According to OSHA, injuries occur at a rate of 158 times per 10,000 workers, making hospitals more hazardous work environments than either construction or manufacturing sites.

National workers’ compensation losses from hospital workers total $2 billion annually, said OSHA assistant secretary Dr. David Michaels.

Musculoskeletal injuries, primarily from lifting and shifting patients, are the single biggest worker injury in hospitals, he said. According to OSHA, 16,680 hospital workers missed work because of a musculoskeletal injury sustained while handling a patient.

"Other hazards facing hospital workers include workplace violence, slips and falls, exposure to chemicals including hazardous drugs, exposure to infectious diseases, and needle sticks," said Dr. Michaels.

As part of a joint effort to promote the website, also on the conference call were Dr. John Howard, director of the National Institute for Occupational Safety and Health, and Dr. Erin DuPree, chief medical officer and vice president of the Joint Commission Center for Transforming Healthcare, and Dr. Lucian Leape, chairman of the Lucian Leape Institute at the National Patient Safety Foundation.

The OSHA website offers educational materials on avoiding injury when handling patients, as well as on workplace safety needs and the implementation of safety and health management systems.

The materials were culled from best practices employed at hospitals around the country deemed by OSHA to be "high-reliability organizations," and include tips such as having a daily "safety huddle" that includes a discussion of "great catches" and "near misses" that occurred during daily operations.

"One of the major barriers in making progress in patient safety is that when people report that they’ve made a mistake, they often get punished for it," said Dr. Leape. "What we’ve been trying to get people to understand is that mistakes happen because of bad systems, not bad people. You have to create an environment where you really believe that, and make it safe for people to talk about their errors so you can understand what you need to fix."

Dr. DuPree said the OSHA resources align with Joint Commission requirements such as those for hospitals to have a written plan for managing environmental safety for patients and all persons in hospitals. The Joint Commission expects that all individuals who work in the hospital should not fear retribution for speaking up about their safety concerns, Dr. DuPree said. "Leaders need to value and empower their workers. They need to understand that fear of reprisal and failure to share knowledge can compromise an organization’s ability to improve safety for all," he said.

As part of its efforts to advise hospital administrators on how to create safer work environments for their employees, the U.S. Department of Labor Occupational Safety and Health Administration has created a list of attributes of what it calls "high-reliability organizations."

Self-assessment tools, tip sheets, and other materials intended to help hospitals become high-reliability organizations (HROs) are available at OSHA's new website, Worker Safety in Hospitals: Caring for our Caregivers.

"The heart of these new materials are real life lessons from high-performing hospitals [that] have implemented best practices to reduce workplace injuries while also improving patient safety," said OSHA assistant secretary Dr. David Michaels in a press briefing.

The website emphasizes principles endorsed by the Joint Commission, particularly the promotion of a "no-blame" culture to destigmatize safety interventions. Operational strategies derived from the distillation of these best practices and endorsed by OSHA include the following:

• Sensitivity to operations. That means hospital workers should know what the standard procedures are, and follow them.

• Reluctance to simplify. This tenet calls upon hospital administrators to explore the larger context in which safety failures occur.

• Preoccupation with failure. OSHA warns administrators to "never let success breed complacency" and impels hospital leaders to "focus unceasingly on ways the system can fail" and to encourage staff to "listen to their ‘inner voice’ of concern."

• Deference to expertise. Pulling rank rather than going to the one who has the most direct experience in a situation is discouraged by OSHA.

• Resilience. Basically, know there will be failures, but hopefully only small ones; learn from them and rebound.

Dr. Michaels, Dr. Howard, Dr. DuPree, and Dr. Leape did not report any relevant financial disclosures.

[email protected]

*This article has been updated 1/16/2014.

Improving hospital worker safety will result in improved patient safety, according to the Occupational Safety and Health Administration, which has unveiled a hospital worker safety online resource center.

Worker Safety in Hospitals: Caring for our Caregivers, OSHA's new website aimed at curbing hospital worker injury rates, was introduced during a media teleconference Jan. 16. According to OSHA, injuries occur at a rate of 158 times per 10,000 workers, making hospitals more hazardous work environments than either construction or manufacturing sites.

National workers’ compensation losses from hospital workers total $2 billion annually, said OSHA assistant secretary Dr. David Michaels.

Musculoskeletal injuries, primarily from lifting and shifting patients, are the single biggest worker injury in hospitals, he said. According to OSHA, 16,680 hospital workers missed work because of a musculoskeletal injury sustained while handling a patient.

"Other hazards facing hospital workers include workplace violence, slips and falls, exposure to chemicals including hazardous drugs, exposure to infectious diseases, and needle sticks," said Dr. Michaels.

As part of a joint effort to promote the website, also on the conference call were Dr. John Howard, director of the National Institute for Occupational Safety and Health, and Dr. Erin DuPree, chief medical officer and vice president of the Joint Commission Center for Transforming Healthcare, and Dr. Lucian Leape, chairman of the Lucian Leape Institute at the National Patient Safety Foundation.

The OSHA website offers educational materials on avoiding injury when handling patients, as well as on workplace safety needs and the implementation of safety and health management systems.

The materials were culled from best practices employed at hospitals around the country deemed by OSHA to be "high-reliability organizations," and include tips such as having a daily "safety huddle" that includes a discussion of "great catches" and "near misses" that occurred during daily operations.

"One of the major barriers in making progress in patient safety is that when people report that they’ve made a mistake, they often get punished for it," said Dr. Leape. "What we’ve been trying to get people to understand is that mistakes happen because of bad systems, not bad people. You have to create an environment where you really believe that, and make it safe for people to talk about their errors so you can understand what you need to fix."

Dr. DuPree said the OSHA resources align with Joint Commission requirements such as those for hospitals to have a written plan for managing environmental safety for patients and all persons in hospitals. The Joint Commission expects that all individuals who work in the hospital should not fear retribution for speaking up about their safety concerns, Dr. DuPree said. "Leaders need to value and empower their workers. They need to understand that fear of reprisal and failure to share knowledge can compromise an organization’s ability to improve safety for all," he said.

As part of its efforts to advise hospital administrators on how to create safer work environments for their employees, the U.S. Department of Labor Occupational Safety and Health Administration has created a list of attributes of what it calls "high-reliability organizations."

Self-assessment tools, tip sheets, and other materials intended to help hospitals become high-reliability organizations (HROs) are available at OSHA's new website, Worker Safety in Hospitals: Caring for our Caregivers.

"The heart of these new materials are real life lessons from high-performing hospitals [that] have implemented best practices to reduce workplace injuries while also improving patient safety," said OSHA assistant secretary Dr. David Michaels in a press briefing.

The website emphasizes principles endorsed by the Joint Commission, particularly the promotion of a "no-blame" culture to destigmatize safety interventions. Operational strategies derived from the distillation of these best practices and endorsed by OSHA include the following:

• Sensitivity to operations. That means hospital workers should know what the standard procedures are, and follow them.

• Reluctance to simplify. This tenet calls upon hospital administrators to explore the larger context in which safety failures occur.

• Preoccupation with failure. OSHA warns administrators to "never let success breed complacency" and impels hospital leaders to "focus unceasingly on ways the system can fail" and to encourage staff to "listen to their ‘inner voice’ of concern."

• Deference to expertise. Pulling rank rather than going to the one who has the most direct experience in a situation is discouraged by OSHA.

• Resilience. Basically, know there will be failures, but hopefully only small ones; learn from them and rebound.

Dr. Michaels, Dr. Howard, Dr. DuPree, and Dr. Leape did not report any relevant financial disclosures.

[email protected]

*This article has been updated 1/16/2014.