Timothy F. Kirn

A new study of children with epilepsy has found that their bone mineral density declines steadily relative to controls, starting perhaps even in the first year of treatment.

The study compared 82 children with epilepsy with 32 age- and sex-matched, first-degree cousins, measuring their bone mineral density (BMD) with dual- energy x-ray absorptiometry. The 82 patients were all ambulatory and without any other conditions that might affect bone density, investigators reported in Neurology. Their ages ranged from 6 to 18 years, with a mean age of 12 years.

The investigators found that the 18 subjects who had had epilepsy less than 1 year had a mean BMD z score of 0.23. The 37 subjects who had epilepsy for 1-5 years had a mean BMD z score of 0.13. And the 27 subjects who had epilepsy for 6 years or longer had a mean BMDz score of 0.06, reported Dr. Raj D. Sheth, director of the Comprehensive Epilepsy Program at the University of Wisconsin, Madison, and colleagues.

By comparison, the control subjects had a mean BMD z score of 0.57.

The difference between the mean score of the control group and the mean score of the subjects who had had epilepsy for less than a year did not reach statistical significance; however, the difference between the controls and the other subjects did.

“These findings suggest that as little as 2 years of treatment could result in significant reductions in BMD,” Dr. Sheth wrote (Neurology 2008;70:170-6).

The study was not able to investigate the role of specific medications in the bone density loss observed, in part because many of the patients had been on more than one drug at some time in their treatment.

Information from adults suggests medication plays a role in bone density loss, but the cause is probably multifactorial, Dr. Sheth said.

The study was able to compare subjects with partial epilepsy with those with generalized epilepsy, however. The investigators found that while those with generalized epilepsy for longer than 1 year had a significantly lower mean z score than controls, those with partial epilepsy had a mean score that was only slightly lower and the difference was not statistically significant.

Interestingly, the study found that calcium intake for the study subjects was somewhat higher than national averages.

Two patients actually experienced a pathologic fracture while the study was underway. The evidence suggests that 40% of fractures that occur in individuals with epilepsy are pathologic; among children with epilepsy, it's 20%, Dr. Sheth said.

One of the fracture patients was a 17-year-old female who fractured her clavicle during a seizure and fractured her leg while walking. She had experienced epilepsy for 15 years and her z score was −3.5. The other patient had had epilepsy for 12 years and had a z score of −2.5. She fractured her arm during a fall.

In an editorial accompanying the study report, Dr. Edwin Trevathan noted that most physicians consider osteopenia and BMD loss to be a problem only for white, postmenopausal women, and patients who smoke, have renal disease, or take corticosteroids (Neurology 2008;70:166-7).

But a previous study found that young adults who have epilepsy have a risk of BMD loss or fracture that is 2-6 times greater than the general population.

“We can probably prevent epilepsy-associated [BMD] loss, and the published data now demand that we make this a priority in epilepsy research and clinical practice,” wrote Dr. Trevathan, who is the director of the National Center on Birth Defects and Developmental Disabilities, at the Centers for Disease Control and Prevention, Atlanta.

“Early intervention shortly after starting treatment for epilepsy among children, adolescents, and young adults should probably be a focus of screening and prevention efforts. Among the elderly with new-onset epilepsy, screening and prevention efforts may need to be started as soon as antiseizure medications are initiated,” he added.

Prophylactic treatment of children with epilepsy with calcium and vitamin D may be useful, but the correct dosage has not yet been determined, Dr. Sheth said.

The study was funded in part by an investigator-initiated grant from GlaxoSmithKline, which makes treatments for epilepsy and osteoporosis.

Dr. Trevathan previously served as an investigator for a Glaxo epilepsy treatment.

ELSEVIER GLOBAL MEDICAL NEWS

A new study of children with epilepsy has found that their bone mineral density declines steadily relative to controls, starting perhaps even in the first year of treatment.

The study compared 82 children with epilepsy with 32 age- and sex-matched, first-degree cousins, measuring their bone mineral density (BMD) with dual- energy x-ray absorptiometry. The 82 patients were all ambulatory and without any other conditions that might affect bone density, investigators reported in Neurology. Their ages ranged from 6 to 18 years, with a mean age of 12 years.

The investigators found that the 18 subjects who had had epilepsy less than 1 year had a mean BMD z score of 0.23. The 37 subjects who had epilepsy for 1-5 years had a mean BMD z score of 0.13. And the 27 subjects who had epilepsy for 6 years or longer had a mean BMDz score of 0.06, reported Dr. Raj D. Sheth, director of the Comprehensive Epilepsy Program at the University of Wisconsin, Madison, and colleagues.

By comparison, the control subjects had a mean BMD z score of 0.57.

The difference between the mean score of the control group and the mean score of the subjects who had had epilepsy for less than a year did not reach statistical significance; however, the difference between the controls and the other subjects did.

“These findings suggest that as little as 2 years of treatment could result in significant reductions in BMD,” Dr. Sheth wrote (Neurology 2008;70:170-6).

The study was not able to investigate the role of specific medications in the bone density loss observed, in part because many of the patients had been on more than one drug at some time in their treatment.

Information from adults suggests medication plays a role in bone density loss, but the cause is probably multifactorial, Dr. Sheth said.

The study was able to compare subjects with partial epilepsy with those with generalized epilepsy, however. The investigators found that while those with generalized epilepsy for longer than 1 year had a significantly lower mean z score than controls, those with partial epilepsy had a mean score that was only slightly lower and the difference was not statistically significant.

Interestingly, the study found that calcium intake for the study subjects was somewhat higher than national averages.

Two patients actually experienced a pathologic fracture while the study was underway. The evidence suggests that 40% of fractures that occur in individuals with epilepsy are pathologic; among children with epilepsy, it's 20%, Dr. Sheth said.

One of the fracture patients was a 17-year-old female who fractured her clavicle during a seizure and fractured her leg while walking. She had experienced epilepsy for 15 years and her z score was −3.5. The other patient had had epilepsy for 12 years and had a z score of −2.5. She fractured her arm during a fall.

In an editorial accompanying the study report, Dr. Edwin Trevathan noted that most physicians consider osteopenia and BMD loss to be a problem only for white, postmenopausal women, and patients who smoke, have renal disease, or take corticosteroids (Neurology 2008;70:166-7).

But a previous study found that young adults who have epilepsy have a risk of BMD loss or fracture that is 2-6 times greater than the general population.

“We can probably prevent epilepsy-associated [BMD] loss, and the published data now demand that we make this a priority in epilepsy research and clinical practice,” wrote Dr. Trevathan, who is the director of the National Center on Birth Defects and Developmental Disabilities, at the Centers for Disease Control and Prevention, Atlanta.

“Early intervention shortly after starting treatment for epilepsy among children, adolescents, and young adults should probably be a focus of screening and prevention efforts. Among the elderly with new-onset epilepsy, screening and prevention efforts may need to be started as soon as antiseizure medications are initiated,” he added.

Prophylactic treatment of children with epilepsy with calcium and vitamin D may be useful, but the correct dosage has not yet been determined, Dr. Sheth said.

The study was funded in part by an investigator-initiated grant from GlaxoSmithKline, which makes treatments for epilepsy and osteoporosis.

Dr. Trevathan previously served as an investigator for a Glaxo epilepsy treatment.

ELSEVIER GLOBAL MEDICAL NEWS

A new study of children with epilepsy has found that their bone mineral density declines steadily relative to controls, starting perhaps even in the first year of treatment.

The study compared 82 children with epilepsy with 32 age- and sex-matched, first-degree cousins, measuring their bone mineral density (BMD) with dual- energy x-ray absorptiometry. The 82 patients were all ambulatory and without any other conditions that might affect bone density, investigators reported in Neurology. Their ages ranged from 6 to 18 years, with a mean age of 12 years.

The investigators found that the 18 subjects who had had epilepsy less than 1 year had a mean BMD z score of 0.23. The 37 subjects who had epilepsy for 1-5 years had a mean BMD z score of 0.13. And the 27 subjects who had epilepsy for 6 years or longer had a mean BMDz score of 0.06, reported Dr. Raj D. Sheth, director of the Comprehensive Epilepsy Program at the University of Wisconsin, Madison, and colleagues.

By comparison, the control subjects had a mean BMD z score of 0.57.

The difference between the mean score of the control group and the mean score of the subjects who had had epilepsy for less than a year did not reach statistical significance; however, the difference between the controls and the other subjects did.

“These findings suggest that as little as 2 years of treatment could result in significant reductions in BMD,” Dr. Sheth wrote (Neurology 2008;70:170-6).

The study was not able to investigate the role of specific medications in the bone density loss observed, in part because many of the patients had been on more than one drug at some time in their treatment.

Information from adults suggests medication plays a role in bone density loss, but the cause is probably multifactorial, Dr. Sheth said.

The study was able to compare subjects with partial epilepsy with those with generalized epilepsy, however. The investigators found that while those with generalized epilepsy for longer than 1 year had a significantly lower mean z score than controls, those with partial epilepsy had a mean score that was only slightly lower and the difference was not statistically significant.

Interestingly, the study found that calcium intake for the study subjects was somewhat higher than national averages.

Two patients actually experienced a pathologic fracture while the study was underway. The evidence suggests that 40% of fractures that occur in individuals with epilepsy are pathologic; among children with epilepsy, it's 20%, Dr. Sheth said.

One of the fracture patients was a 17-year-old female who fractured her clavicle during a seizure and fractured her leg while walking. She had experienced epilepsy for 15 years and her z score was −3.5. The other patient had had epilepsy for 12 years and had a z score of −2.5. She fractured her arm during a fall.

In an editorial accompanying the study report, Dr. Edwin Trevathan noted that most physicians consider osteopenia and BMD loss to be a problem only for white, postmenopausal women, and patients who smoke, have renal disease, or take corticosteroids (Neurology 2008;70:166-7).

But a previous study found that young adults who have epilepsy have a risk of BMD loss or fracture that is 2-6 times greater than the general population.

“We can probably prevent epilepsy-associated [BMD] loss, and the published data now demand that we make this a priority in epilepsy research and clinical practice,” wrote Dr. Trevathan, who is the director of the National Center on Birth Defects and Developmental Disabilities, at the Centers for Disease Control and Prevention, Atlanta.

“Early intervention shortly after starting treatment for epilepsy among children, adolescents, and young adults should probably be a focus of screening and prevention efforts. Among the elderly with new-onset epilepsy, screening and prevention efforts may need to be started as soon as antiseizure medications are initiated,” he added.

Prophylactic treatment of children with epilepsy with calcium and vitamin D may be useful, but the correct dosage has not yet been determined, Dr. Sheth said.

The study was funded in part by an investigator-initiated grant from GlaxoSmithKline, which makes treatments for epilepsy and osteoporosis.

Dr. Trevathan previously served as an investigator for a Glaxo epilepsy treatment.

ELSEVIER GLOBAL MEDICAL NEWS

Manual aspiration of atherothrombotic debris during percutaneous coronary intervention improved myocardial reperfusion and decreased ST-segment elevation, compared with PCI alone in a randomized controlled trial of patients with possible MIs.

After conventional PCI, 26% of patients had a myocardial blush grade of 0 or 1; but after PCI with thrombus aspiration, 17% of patients had grades of 0 or 1, reported Dr. Tone Svilaas and his colleagues, from the University Medical Center Groningen, the Netherlands. A 70% or greater resolution of ST-segment elevation was seen in 57% of the patients treated with aspiration and in 44% of the patients treated with ballooning and stent placement alone (N. Engl. J. Med. 2008;358:557–67).

Deaths and major cardiac events at 30 days were significantly related to myocardial blush grade and resolution of ST-segment elevation. At 30 days, 2% of the aspiration group and 4% of the conventional PCI group had died and 4% and 3%, respectively, had a major bleeding event. Major adverse cardiac events occurred in 7% and 9%, respectively.

All patients can potentially benefit from aspiration, they said. “Our data show that angiographic variables such as TIMI flow or the presence of visible thrombus are not predictors of patients in whom aspiration will be effective.”

In a commentary accompanying the report, Dr. George W. Vetrovec said thrombus extraction is “conceptually sound and appears to reduce the risk.” In an interview, however, Dr. Vetrovec of the Virginia Commonwealth University, Richmond, Pauley Heart Center expressed concern about the impact of the additional process on door-to-balloon time. Although aspiration has not increased door-to-balloon time in his personal experience, widespread use might be associated with longer times, and that possibility needs to be evaluated, he said.

For their study, Dr. Svilaas and his colleagues enrolled 1,071 consecutive patients with a possible MI with ST-segment elevation seen at the center during 2005–2006. All had symptoms lasting more than 30 minutes, an onset lasting less than 12 hours, and an ST-segment elevation of more than 0.1 mV in two or more leads on ECG. The mean age of the patients was 63 years, and about 70% were male.

Patients were randomized prior to angiography. All had a guidewire introduced through their occlusion. The patients who received aspiration PCI had a 6-French Export Aspiration Catheter (Medtronic) advanced into the coronary segment during continuous aspiration.

The median time from baseline to postprocedural ECG was 44 minutes for the aspiration group and 43 minutes for the conventional PCI group.

An examination of the aspiration contents indicated atherothrombotic material was present in 73% of the 454 aspiration cases examined. The contents consisted of platelets alone in 68% of cases, a thrombus with bands of erythrocytes in 15% of cases, and a thrombus with various components in 17% of cases.

Manual aspiration of atherothrombotic debris during percutaneous coronary intervention improved myocardial reperfusion and decreased ST-segment elevation, compared with PCI alone in a randomized controlled trial of patients with possible MIs.

After conventional PCI, 26% of patients had a myocardial blush grade of 0 or 1; but after PCI with thrombus aspiration, 17% of patients had grades of 0 or 1, reported Dr. Tone Svilaas and his colleagues, from the University Medical Center Groningen, the Netherlands. A 70% or greater resolution of ST-segment elevation was seen in 57% of the patients treated with aspiration and in 44% of the patients treated with ballooning and stent placement alone (N. Engl. J. Med. 2008;358:557–67).

Deaths and major cardiac events at 30 days were significantly related to myocardial blush grade and resolution of ST-segment elevation. At 30 days, 2% of the aspiration group and 4% of the conventional PCI group had died and 4% and 3%, respectively, had a major bleeding event. Major adverse cardiac events occurred in 7% and 9%, respectively.

All patients can potentially benefit from aspiration, they said. “Our data show that angiographic variables such as TIMI flow or the presence of visible thrombus are not predictors of patients in whom aspiration will be effective.”

In a commentary accompanying the report, Dr. George W. Vetrovec said thrombus extraction is “conceptually sound and appears to reduce the risk.” In an interview, however, Dr. Vetrovec of the Virginia Commonwealth University, Richmond, Pauley Heart Center expressed concern about the impact of the additional process on door-to-balloon time. Although aspiration has not increased door-to-balloon time in his personal experience, widespread use might be associated with longer times, and that possibility needs to be evaluated, he said.

For their study, Dr. Svilaas and his colleagues enrolled 1,071 consecutive patients with a possible MI with ST-segment elevation seen at the center during 2005–2006. All had symptoms lasting more than 30 minutes, an onset lasting less than 12 hours, and an ST-segment elevation of more than 0.1 mV in two or more leads on ECG. The mean age of the patients was 63 years, and about 70% were male.

Patients were randomized prior to angiography. All had a guidewire introduced through their occlusion. The patients who received aspiration PCI had a 6-French Export Aspiration Catheter (Medtronic) advanced into the coronary segment during continuous aspiration.

The median time from baseline to postprocedural ECG was 44 minutes for the aspiration group and 43 minutes for the conventional PCI group.

An examination of the aspiration contents indicated atherothrombotic material was present in 73% of the 454 aspiration cases examined. The contents consisted of platelets alone in 68% of cases, a thrombus with bands of erythrocytes in 15% of cases, and a thrombus with various components in 17% of cases.

Manual aspiration of atherothrombotic debris during percutaneous coronary intervention improved myocardial reperfusion and decreased ST-segment elevation, compared with PCI alone in a randomized controlled trial of patients with possible MIs.

After conventional PCI, 26% of patients had a myocardial blush grade of 0 or 1; but after PCI with thrombus aspiration, 17% of patients had grades of 0 or 1, reported Dr. Tone Svilaas and his colleagues, from the University Medical Center Groningen, the Netherlands. A 70% or greater resolution of ST-segment elevation was seen in 57% of the patients treated with aspiration and in 44% of the patients treated with ballooning and stent placement alone (N. Engl. J. Med. 2008;358:557–67).

Deaths and major cardiac events at 30 days were significantly related to myocardial blush grade and resolution of ST-segment elevation. At 30 days, 2% of the aspiration group and 4% of the conventional PCI group had died and 4% and 3%, respectively, had a major bleeding event. Major adverse cardiac events occurred in 7% and 9%, respectively.

All patients can potentially benefit from aspiration, they said. “Our data show that angiographic variables such as TIMI flow or the presence of visible thrombus are not predictors of patients in whom aspiration will be effective.”

In a commentary accompanying the report, Dr. George W. Vetrovec said thrombus extraction is “conceptually sound and appears to reduce the risk.” In an interview, however, Dr. Vetrovec of the Virginia Commonwealth University, Richmond, Pauley Heart Center expressed concern about the impact of the additional process on door-to-balloon time. Although aspiration has not increased door-to-balloon time in his personal experience, widespread use might be associated with longer times, and that possibility needs to be evaluated, he said.

For their study, Dr. Svilaas and his colleagues enrolled 1,071 consecutive patients with a possible MI with ST-segment elevation seen at the center during 2005–2006. All had symptoms lasting more than 30 minutes, an onset lasting less than 12 hours, and an ST-segment elevation of more than 0.1 mV in two or more leads on ECG. The mean age of the patients was 63 years, and about 70% were male.

Patients were randomized prior to angiography. All had a guidewire introduced through their occlusion. The patients who received aspiration PCI had a 6-French Export Aspiration Catheter (Medtronic) advanced into the coronary segment during continuous aspiration.

The median time from baseline to postprocedural ECG was 44 minutes for the aspiration group and 43 minutes for the conventional PCI group.

An examination of the aspiration contents indicated atherothrombotic material was present in 73% of the 454 aspiration cases examined. The contents consisted of platelets alone in 68% of cases, a thrombus with bands of erythrocytes in 15% of cases, and a thrombus with various components in 17% of cases.

Oral sucrose is known to be an effective analgesic for neonates and infants undergoing painful procedures. Now a new study has shown that sucrose significantly decreases pain and distress when given to infants before immunizations.

The study comprised 83 infants, aged 2 months and 4 months. The infants were randomized, with careful blinding of the investigators and parents, to either 24% oral sucrose or to sterile water, just before receiving a series of three immunization injections.

The results showed a 60% decrease in the mean pain score after the first injection for the 38 infants given sucrose, compared with the mean score of the 45 infants given sterile water, and a 78% decrease in the mean pain score at 2 minutes after the third injection, reported Linda A. Hatfield, Ph.D., of Pennsylvania State University, University Park, and her colleagues.

The highest mean pain scores for both groups of infants were seen at the pain assessment at 7 minutes, which was immediately after the third injection, Dr. Hatfield and colleagues reported (Pediatrics 2008;121:e327–34). At that point, the sucrose group had a mean pain score 21% lower than controls. And 2 minutes after that last injection, when the difference in the mean pain scores was 78%, the sucrose-treated group had returned to showing no pain response.

The pain scale used in the study was the University of Wisconsin Children's Hospital Pain Scale, which uses five criteria to score pain responses: cry, facial expression, behavioral, body movement, and sleep.

The 24% sucrose solution was delivered orally from a syringe, after which the infants were given a pacifier to suck. The dose given was 0.6 mL/kg, with the weight based on the average birth weight, and therefore equaled about a 2-mL dose.

The immunizations given were a combined diphtheria, tetanus, acellular pertussis, hepatitis B, and polio vaccine; a Haemophilus influenzae type B vaccine; and the heptavalent pneumococcal conjugate vaccine. Each was given 2 minutes apart.

Dr. Hatfield and her colleagues noted that sucrose already has been shown to be an effective analgesic for term and preterm infants having venipuncture and heel lance procedures, and that the American Academy of Pediatrics recommends sucrose for minor painful procedures in neonates.

They also noted that it works very quickly, so that it can be given just 2 minutes before any procedure or injection.

Based on the pain scores from their study, the number needed to treat to have one infant who showed minimal distress—wincing, but easy to console—at 2 minutes after sucrose administration was four. The number needed to treat to have one infant with minimal distress 2 minutes after a third injection was two.

“Thus, pediatric care providers would need only a small number of infants to document the efficacy of oral sucrose in reducing pain associated with immunization,” Dr. Hatfield and her colleagues said.

The authors reported that they had no financial relationships to disclose.

Oral sucrose is known to be an effective analgesic for neonates and infants undergoing painful procedures. Now a new study has shown that sucrose significantly decreases pain and distress when given to infants before immunizations.

The study comprised 83 infants, aged 2 months and 4 months. The infants were randomized, with careful blinding of the investigators and parents, to either 24% oral sucrose or to sterile water, just before receiving a series of three immunization injections.

The results showed a 60% decrease in the mean pain score after the first injection for the 38 infants given sucrose, compared with the mean score of the 45 infants given sterile water, and a 78% decrease in the mean pain score at 2 minutes after the third injection, reported Linda A. Hatfield, Ph.D., of Pennsylvania State University, University Park, and her colleagues.

The highest mean pain scores for both groups of infants were seen at the pain assessment at 7 minutes, which was immediately after the third injection, Dr. Hatfield and colleagues reported (Pediatrics 2008;121:e327–34). At that point, the sucrose group had a mean pain score 21% lower than controls. And 2 minutes after that last injection, when the difference in the mean pain scores was 78%, the sucrose-treated group had returned to showing no pain response.

The pain scale used in the study was the University of Wisconsin Children's Hospital Pain Scale, which uses five criteria to score pain responses: cry, facial expression, behavioral, body movement, and sleep.

The 24% sucrose solution was delivered orally from a syringe, after which the infants were given a pacifier to suck. The dose given was 0.6 mL/kg, with the weight based on the average birth weight, and therefore equaled about a 2-mL dose.

The immunizations given were a combined diphtheria, tetanus, acellular pertussis, hepatitis B, and polio vaccine; a Haemophilus influenzae type B vaccine; and the heptavalent pneumococcal conjugate vaccine. Each was given 2 minutes apart.

Dr. Hatfield and her colleagues noted that sucrose already has been shown to be an effective analgesic for term and preterm infants having venipuncture and heel lance procedures, and that the American Academy of Pediatrics recommends sucrose for minor painful procedures in neonates.

They also noted that it works very quickly, so that it can be given just 2 minutes before any procedure or injection.

Based on the pain scores from their study, the number needed to treat to have one infant who showed minimal distress—wincing, but easy to console—at 2 minutes after sucrose administration was four. The number needed to treat to have one infant with minimal distress 2 minutes after a third injection was two.

“Thus, pediatric care providers would need only a small number of infants to document the efficacy of oral sucrose in reducing pain associated with immunization,” Dr. Hatfield and her colleagues said.

The authors reported that they had no financial relationships to disclose.

Oral sucrose is known to be an effective analgesic for neonates and infants undergoing painful procedures. Now a new study has shown that sucrose significantly decreases pain and distress when given to infants before immunizations.

The study comprised 83 infants, aged 2 months and 4 months. The infants were randomized, with careful blinding of the investigators and parents, to either 24% oral sucrose or to sterile water, just before receiving a series of three immunization injections.

The results showed a 60% decrease in the mean pain score after the first injection for the 38 infants given sucrose, compared with the mean score of the 45 infants given sterile water, and a 78% decrease in the mean pain score at 2 minutes after the third injection, reported Linda A. Hatfield, Ph.D., of Pennsylvania State University, University Park, and her colleagues.

The highest mean pain scores for both groups of infants were seen at the pain assessment at 7 minutes, which was immediately after the third injection, Dr. Hatfield and colleagues reported (Pediatrics 2008;121:e327–34). At that point, the sucrose group had a mean pain score 21% lower than controls. And 2 minutes after that last injection, when the difference in the mean pain scores was 78%, the sucrose-treated group had returned to showing no pain response.

The pain scale used in the study was the University of Wisconsin Children's Hospital Pain Scale, which uses five criteria to score pain responses: cry, facial expression, behavioral, body movement, and sleep.

The 24% sucrose solution was delivered orally from a syringe, after which the infants were given a pacifier to suck. The dose given was 0.6 mL/kg, with the weight based on the average birth weight, and therefore equaled about a 2-mL dose.

The immunizations given were a combined diphtheria, tetanus, acellular pertussis, hepatitis B, and polio vaccine; a Haemophilus influenzae type B vaccine; and the heptavalent pneumococcal conjugate vaccine. Each was given 2 minutes apart.

Dr. Hatfield and her colleagues noted that sucrose already has been shown to be an effective analgesic for term and preterm infants having venipuncture and heel lance procedures, and that the American Academy of Pediatrics recommends sucrose for minor painful procedures in neonates.

They also noted that it works very quickly, so that it can be given just 2 minutes before any procedure or injection.

Based on the pain scores from their study, the number needed to treat to have one infant who showed minimal distress—wincing, but easy to console—at 2 minutes after sucrose administration was four. The number needed to treat to have one infant with minimal distress 2 minutes after a third injection was two.

“Thus, pediatric care providers would need only a small number of infants to document the efficacy of oral sucrose in reducing pain associated with immunization,” Dr. Hatfield and her colleagues said.

The authors reported that they had no financial relationships to disclose.

The blood glucose excursion that patients with type 2 diabetes experience after a meal correlates strongly with their carotid intima-media thickness, a marker for cardiovascular disease, reported Italian researchers in a large, ongoing study.

The research also showed that the rise in blood glucose level after a meal almost always peaks at about 1 hour, even though 2 hours is the time usually used for measuring postprandial response in patients with diabetes, reported Dr. Katherine Esposito of the division of metabolic diseases at the Second University of Naples (Italy), and colleagues from the Second University and the University of Warwick (England) (J. Clin. Endocrinol. Metab. 2008 Jan. 15 [Epub doi:10.1210/jc.2007–2000

The timing of the peak in blood glucose does not appear to be affected by how the diabetes is being treated—that is, with diet or with oral drugs, they wrote.

The American Diabetes Association currently does not recommend that patients monitor postprandial glucose, they noted. But this study—which, along with other studies, showed a correlation between postprandial glucose and a marker for cardiovascular disease—suggests there may be some benefit.

Large epidemiological studies have reported a strong association between hyperglycemia after a meal and cardiovascular risk; an accumulating body of evidence indicates an association between postmeal hyperglycemia and oxidative stress, atherosclerosis, and endothelial dysfunction, all of which are features of cardiovascular disease, according to the investigators.

This analysis used data on 644 patients enrolled in the ongoing study who measured their blood glucose levels at home half an hour before their biggest meal of the day, and then four times after the meal, half an hour apart, on three separate occasions. The patients also had their carotid intima-media thickness measured by ultrasonography. They had been diagnosed with type 2 diabetes at least 6 months prior to enrollment and had had diabetes for not more than 10 years. Their mean age was 57 years, their mean body mass index was 29.8 kg/m

When the patients were grouped into quintiles, based on their averaged maximal incremental glucose peaks after meals, hemoglobin A_1c levels and carotid intima-media thickness increased progressively. In the lowest quintile, in which the incremental glucose peak was from 0 to 40 mg/dL, the mean carotid intima-media thickness was 0.82 mm. In the highest quintile, in which the peak was greater than 130 mg/dL, the mean thickness was 0.94 mm.

Statistical analysis showed that when all glucose parameters were considered, including fasting glucose and HbA_1c, the incremental glucose peak had the highest correlation.

In addition, data from the measurements taken before the meals and at different times afterward showed that 95% of the patients had their highest glucose peak at 1 hour after the meals.

The 343 patients who were on drug therapy, rather than on a prescribed diet alone, tended to fall into the higher quintiles of incremental glucose peak. However, the patients on drug therapy did not differ from the patients on diet therapy in the timing of their glucose peak.

The study also discovered that serious excursions in blood glucose after a meal occurred in the majority of the subjects.

Two-thirds of the patients had incremental glucose peaks that exceeded 50 mg/dL, and at some time after the meals, 94% of patients recorded a glucose level that exceeded 159 mg/dL, which is the American Diabetes Association's acceptable threshold for postprandial glucose, the researchers wrote, noting that other studies have shown that drug treatment that targets postprandial glucose increases can affect cardiovascular risk and carotid intima-media thickness.

In one of those studies, which Dr. Esposito conducted, 175 drug-naive patients with type 2 diabetes were randomized to receive either repaglinide, a rapid-acting secretagogue that targets postprandial glucose, or glyburide. Of those assigned to repaglinide, 52% had a regression in their carotid intima-media thickness greater than 0.02 mm, compared with 18% of those assigned glyburide (Circulation 2004;110:214–9).

In this recent study, Dr. Esposito and her colleagues declared that they had no conflicts of interest.

The blood glucose excursion that patients with type 2 diabetes experience after a meal correlates strongly with their carotid intima-media thickness, a marker for cardiovascular disease, reported Italian researchers in a large, ongoing study.

The research also showed that the rise in blood glucose level after a meal almost always peaks at about 1 hour, even though 2 hours is the time usually used for measuring postprandial response in patients with diabetes, reported Dr. Katherine Esposito of the division of metabolic diseases at the Second University of Naples (Italy), and colleagues from the Second University and the University of Warwick (England) (J. Clin. Endocrinol. Metab. 2008 Jan. 15 [Epub doi:10.1210/jc.2007–2000

The timing of the peak in blood glucose does not appear to be affected by how the diabetes is being treated—that is, with diet or with oral drugs, they wrote.

The American Diabetes Association currently does not recommend that patients monitor postprandial glucose, they noted. But this study—which, along with other studies, showed a correlation between postprandial glucose and a marker for cardiovascular disease—suggests there may be some benefit.

Large epidemiological studies have reported a strong association between hyperglycemia after a meal and cardiovascular risk; an accumulating body of evidence indicates an association between postmeal hyperglycemia and oxidative stress, atherosclerosis, and endothelial dysfunction, all of which are features of cardiovascular disease, according to the investigators.

This analysis used data on 644 patients enrolled in the ongoing study who measured their blood glucose levels at home half an hour before their biggest meal of the day, and then four times after the meal, half an hour apart, on three separate occasions. The patients also had their carotid intima-media thickness measured by ultrasonography. They had been diagnosed with type 2 diabetes at least 6 months prior to enrollment and had had diabetes for not more than 10 years. Their mean age was 57 years, their mean body mass index was 29.8 kg/m

When the patients were grouped into quintiles, based on their averaged maximal incremental glucose peaks after meals, hemoglobin A_1c levels and carotid intima-media thickness increased progressively. In the lowest quintile, in which the incremental glucose peak was from 0 to 40 mg/dL, the mean carotid intima-media thickness was 0.82 mm. In the highest quintile, in which the peak was greater than 130 mg/dL, the mean thickness was 0.94 mm.

Statistical analysis showed that when all glucose parameters were considered, including fasting glucose and HbA_1c, the incremental glucose peak had the highest correlation.

In addition, data from the measurements taken before the meals and at different times afterward showed that 95% of the patients had their highest glucose peak at 1 hour after the meals.

The 343 patients who were on drug therapy, rather than on a prescribed diet alone, tended to fall into the higher quintiles of incremental glucose peak. However, the patients on drug therapy did not differ from the patients on diet therapy in the timing of their glucose peak.

The study also discovered that serious excursions in blood glucose after a meal occurred in the majority of the subjects.

Two-thirds of the patients had incremental glucose peaks that exceeded 50 mg/dL, and at some time after the meals, 94% of patients recorded a glucose level that exceeded 159 mg/dL, which is the American Diabetes Association's acceptable threshold for postprandial glucose, the researchers wrote, noting that other studies have shown that drug treatment that targets postprandial glucose increases can affect cardiovascular risk and carotid intima-media thickness.

In one of those studies, which Dr. Esposito conducted, 175 drug-naive patients with type 2 diabetes were randomized to receive either repaglinide, a rapid-acting secretagogue that targets postprandial glucose, or glyburide. Of those assigned to repaglinide, 52% had a regression in their carotid intima-media thickness greater than 0.02 mm, compared with 18% of those assigned glyburide (Circulation 2004;110:214–9).

In this recent study, Dr. Esposito and her colleagues declared that they had no conflicts of interest.

The blood glucose excursion that patients with type 2 diabetes experience after a meal correlates strongly with their carotid intima-media thickness, a marker for cardiovascular disease, reported Italian researchers in a large, ongoing study.

The research also showed that the rise in blood glucose level after a meal almost always peaks at about 1 hour, even though 2 hours is the time usually used for measuring postprandial response in patients with diabetes, reported Dr. Katherine Esposito of the division of metabolic diseases at the Second University of Naples (Italy), and colleagues from the Second University and the University of Warwick (England) (J. Clin. Endocrinol. Metab. 2008 Jan. 15 [Epub doi:10.1210/jc.2007–2000

The timing of the peak in blood glucose does not appear to be affected by how the diabetes is being treated—that is, with diet or with oral drugs, they wrote.

The American Diabetes Association currently does not recommend that patients monitor postprandial glucose, they noted. But this study—which, along with other studies, showed a correlation between postprandial glucose and a marker for cardiovascular disease—suggests there may be some benefit.

Large epidemiological studies have reported a strong association between hyperglycemia after a meal and cardiovascular risk; an accumulating body of evidence indicates an association between postmeal hyperglycemia and oxidative stress, atherosclerosis, and endothelial dysfunction, all of which are features of cardiovascular disease, according to the investigators.

This analysis used data on 644 patients enrolled in the ongoing study who measured their blood glucose levels at home half an hour before their biggest meal of the day, and then four times after the meal, half an hour apart, on three separate occasions. The patients also had their carotid intima-media thickness measured by ultrasonography. They had been diagnosed with type 2 diabetes at least 6 months prior to enrollment and had had diabetes for not more than 10 years. Their mean age was 57 years, their mean body mass index was 29.8 kg/m

When the patients were grouped into quintiles, based on their averaged maximal incremental glucose peaks after meals, hemoglobin A_1c levels and carotid intima-media thickness increased progressively. In the lowest quintile, in which the incremental glucose peak was from 0 to 40 mg/dL, the mean carotid intima-media thickness was 0.82 mm. In the highest quintile, in which the peak was greater than 130 mg/dL, the mean thickness was 0.94 mm.

Statistical analysis showed that when all glucose parameters were considered, including fasting glucose and HbA_1c, the incremental glucose peak had the highest correlation.

In addition, data from the measurements taken before the meals and at different times afterward showed that 95% of the patients had their highest glucose peak at 1 hour after the meals.

The 343 patients who were on drug therapy, rather than on a prescribed diet alone, tended to fall into the higher quintiles of incremental glucose peak. However, the patients on drug therapy did not differ from the patients on diet therapy in the timing of their glucose peak.

The study also discovered that serious excursions in blood glucose after a meal occurred in the majority of the subjects.

Two-thirds of the patients had incremental glucose peaks that exceeded 50 mg/dL, and at some time after the meals, 94% of patients recorded a glucose level that exceeded 159 mg/dL, which is the American Diabetes Association's acceptable threshold for postprandial glucose, the researchers wrote, noting that other studies have shown that drug treatment that targets postprandial glucose increases can affect cardiovascular risk and carotid intima-media thickness.

In one of those studies, which Dr. Esposito conducted, 175 drug-naive patients with type 2 diabetes were randomized to receive either repaglinide, a rapid-acting secretagogue that targets postprandial glucose, or glyburide. Of those assigned to repaglinide, 52% had a regression in their carotid intima-media thickness greater than 0.02 mm, compared with 18% of those assigned glyburide (Circulation 2004;110:214–9).

In this recent study, Dr. Esposito and her colleagues declared that they had no conflicts of interest.

Diet soda, meat, and fried foods are associated with the development of metabolic syndrome, researchers from the Atherosclerosis Risk in Communities Study reported.

The study, which gathered dietary information on 9,514 individuals, then followed them for 9 years, found that the single food item with the strongest association to development of the metabolic syndrome was diet soda, with those who consumed an average of one serving a day having a 34% greater risk of developing metabolic syndrome than those who drank none.

The next strongest association was with meat consumption, with a 25% greater risk, according to the study.

Dairy intake had a beneficial effect, with a hazard ratio of 0.87, or a reduction in risk of 13%, reported Pamela L. Lutsey of the division of epidemiology and community health at the University of Minnesota, Minneapolis, and colleagues (Circulation 2008;117:754–61).

Previous studies of the contribution of diet and specific foods to metabolic syndrome have tended to focus on a single food group and to be cross-sectional survey studies. So a particular strength of this study was its prospective design, “which overcomes a variety of limitations common to cross-sectional data,” Ms. Lutsey noted.

Twenty percent of the subjects had metabolic syndrome at the start of the study, when they were given the first of two diet surveys. At the end of 9 years, another 40% had developed the syndrome. That 60% rate of metabolic syndrome “foreshadows a worrisome trend for the burden of [metabolic syndrome] in the United States,” Ms. Lutsey wrote.

The patients followed in the study were all middle aged, with a mean age of 54 years, and 56% were female.

The data showed that a Western style diet—high intakes of refined grains, processed meat, fried foods, and red meat—was associated with greater risk of metabolic syndrome. Those in the group who had the highest Western-diet consumption pattern had an 18% greater risk than did those with the lowest pattern.

Fried foods were associated with a 25% greater risk.

The investigators expected to find, but did not, that a prudent diet—heavy in whole grains, fruits, vegetables, and fish—was protective. They found no association between metabolic syndrome and this pattern of eating, though previous studies have found an association, and, in particular, a benefit. The hazard ratio was 1.07, and was not statistically significant. Likewise, consumption of sweetened beverages and of coffee was not found to be associated with metabolic syndrome.

The finding of the association between diet soda and metabolic syndrome has been made before. The Framingham Heart Study reported a 56% increase in risk in those who consumed one or more servings per day. Another investigation found that persons with diabetes who drank diet soda had poorer glucose control than did those who consumed none.

“Additional research on the relation between diet soda and incident [metabolic syndrome] is clearly warranted,” Ms. Lutsey wrote.

Diet soda, meat, and fried foods are associated with the development of metabolic syndrome, researchers from the Atherosclerosis Risk in Communities Study reported.

The study, which gathered dietary information on 9,514 individuals, then followed them for 9 years, found that the single food item with the strongest association to development of the metabolic syndrome was diet soda, with those who consumed an average of one serving a day having a 34% greater risk of developing metabolic syndrome than those who drank none.

The next strongest association was with meat consumption, with a 25% greater risk, according to the study.

Dairy intake had a beneficial effect, with a hazard ratio of 0.87, or a reduction in risk of 13%, reported Pamela L. Lutsey of the division of epidemiology and community health at the University of Minnesota, Minneapolis, and colleagues (Circulation 2008;117:754–61).

Previous studies of the contribution of diet and specific foods to metabolic syndrome have tended to focus on a single food group and to be cross-sectional survey studies. So a particular strength of this study was its prospective design, “which overcomes a variety of limitations common to cross-sectional data,” Ms. Lutsey noted.

Twenty percent of the subjects had metabolic syndrome at the start of the study, when they were given the first of two diet surveys. At the end of 9 years, another 40% had developed the syndrome. That 60% rate of metabolic syndrome “foreshadows a worrisome trend for the burden of [metabolic syndrome] in the United States,” Ms. Lutsey wrote.

The patients followed in the study were all middle aged, with a mean age of 54 years, and 56% were female.

The data showed that a Western style diet—high intakes of refined grains, processed meat, fried foods, and red meat—was associated with greater risk of metabolic syndrome. Those in the group who had the highest Western-diet consumption pattern had an 18% greater risk than did those with the lowest pattern.

Fried foods were associated with a 25% greater risk.

The investigators expected to find, but did not, that a prudent diet—heavy in whole grains, fruits, vegetables, and fish—was protective. They found no association between metabolic syndrome and this pattern of eating, though previous studies have found an association, and, in particular, a benefit. The hazard ratio was 1.07, and was not statistically significant. Likewise, consumption of sweetened beverages and of coffee was not found to be associated with metabolic syndrome.

The finding of the association between diet soda and metabolic syndrome has been made before. The Framingham Heart Study reported a 56% increase in risk in those who consumed one or more servings per day. Another investigation found that persons with diabetes who drank diet soda had poorer glucose control than did those who consumed none.

“Additional research on the relation between diet soda and incident [metabolic syndrome] is clearly warranted,” Ms. Lutsey wrote.

Diet soda, meat, and fried foods are associated with the development of metabolic syndrome, researchers from the Atherosclerosis Risk in Communities Study reported.

The study, which gathered dietary information on 9,514 individuals, then followed them for 9 years, found that the single food item with the strongest association to development of the metabolic syndrome was diet soda, with those who consumed an average of one serving a day having a 34% greater risk of developing metabolic syndrome than those who drank none.

The next strongest association was with meat consumption, with a 25% greater risk, according to the study.

Dairy intake had a beneficial effect, with a hazard ratio of 0.87, or a reduction in risk of 13%, reported Pamela L. Lutsey of the division of epidemiology and community health at the University of Minnesota, Minneapolis, and colleagues (Circulation 2008;117:754–61).

Previous studies of the contribution of diet and specific foods to metabolic syndrome have tended to focus on a single food group and to be cross-sectional survey studies. So a particular strength of this study was its prospective design, “which overcomes a variety of limitations common to cross-sectional data,” Ms. Lutsey noted.

Twenty percent of the subjects had metabolic syndrome at the start of the study, when they were given the first of two diet surveys. At the end of 9 years, another 40% had developed the syndrome. That 60% rate of metabolic syndrome “foreshadows a worrisome trend for the burden of [metabolic syndrome] in the United States,” Ms. Lutsey wrote.

The patients followed in the study were all middle aged, with a mean age of 54 years, and 56% were female.

The data showed that a Western style diet—high intakes of refined grains, processed meat, fried foods, and red meat—was associated with greater risk of metabolic syndrome. Those in the group who had the highest Western-diet consumption pattern had an 18% greater risk than did those with the lowest pattern.

Fried foods were associated with a 25% greater risk.

The investigators expected to find, but did not, that a prudent diet—heavy in whole grains, fruits, vegetables, and fish—was protective. They found no association between metabolic syndrome and this pattern of eating, though previous studies have found an association, and, in particular, a benefit. The hazard ratio was 1.07, and was not statistically significant. Likewise, consumption of sweetened beverages and of coffee was not found to be associated with metabolic syndrome.

The finding of the association between diet soda and metabolic syndrome has been made before. The Framingham Heart Study reported a 56% increase in risk in those who consumed one or more servings per day. Another investigation found that persons with diabetes who drank diet soda had poorer glucose control than did those who consumed none.

“Additional research on the relation between diet soda and incident [metabolic syndrome] is clearly warranted,” Ms. Lutsey wrote.

SALT LAKE CITY – Narcotic bowel syndrome is a problem that physicians have been sweeping under the rug, and it may be growing in frequency, Dr. Douglas A. Drossman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Physicians have ignored this syndrome, since many are loathe to undertake the arduous task of weaning their patients from narcotics, said Dr. Drossman, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders.

But this reluctance is not necessary, because patients can be helped to break the “vicious cycle,” he said. There is a very effective protocol that can be used to withdraw patients from narcotics, using clonidine for the physical withdrawal symptoms and lorazepam for the anxiety, while switching them to an antidepressant for pain control.

This syndrome was first noted and described in the 1980s, but very little has been written about it, Dr. Drossman said. Since the 1980s, almost nothing has been published on the topic until recently, when Dr. Drossman and his colleagues Dr. David Grunkemeier, Dr. Joseph Cassara, and Ms. Christine Dalton published a paper (Clin. Gastroenterol. Hepatol. 2007;5:1126–39).

He has seen at least 100 patients with narcotic bowel syndrome in his clinic.

Typically, the patient with narcotic bowel syndrome was started on an opiate because of a functional bowel disorder, or after surgery, or even for an acute painful condition. The patient then developed chronic or intermittent colicky abdominal pain, often due to delayed motility.

At first, the narcotic helps this pain, but over time tachyphylaxis and hyperalgesia set in, rendering the narcotic less and less effective and making the patient dependent on ever-escalating doses.

Dr. Drossman likened the situation to using alcohol to treat a patient with delirium tremens. The alcohol relieves the acute symptoms, but it also perpetuates the cycle.

Dr. Drossman, a gastroenterologist who is trained in psychosomatic medicine, said narcotic bowel syndrome often gets pushed to the background. Narcotics are prescribed because that's what the patient wants, and clinics and hospitals pressure physicians to move patients through the system fast.

The doctors do not have the time or the motivation to address such a complex problem in a medical system that dictates quick processing of patients, Dr. Drossman said.

Narcotic bowel syndrome is probably a U.S. phenomenon, since narcotics are not used as frequently in the rest of the world. About 80% of the world's medical use of narcotics occurs in the United States, and physicians here are using opiates more and more, he said.

According to the protocol Dr. Drossman recommends, physicians who want to detoxify a patient should start with a tricyclic antidepressant or a serotonin-noradrenergic inhibitor, which is begun about 2 days before the withdrawal is initiated. Of the tricyclics, desipramine or nortriptyline are better than imipramine or amitriptyline because they have fewer side effects, he said.

A low dose is used for pain control, for example 50 mg per day of desipramine taken at bedtime, which is titrated up to 150 mg per day.

One day before narcotic withdrawal begins, lorazepam is started in order to ease anxiety, at a dose of 1 mg every 6–8 hours, continued throughout the entire withdrawal.

The narcotic can be withdrawn at a rate of 10%–33% per day, meaning the detoxification can take anywhere from 3 to 10 days.

On the second or third day of the withdrawal, clonidine is begun to treat the sympathetic-related symptoms, such as muscle pains and chills. Both the lorazepam and the clonidine can be tapered and discontinued once the withdrawal is complete.

If the patient is constipated, he or she can be treated with polyethylene glycol. The antidepressant is continued indefinitely, as needed, for pain control.

Dr. Drossman is on the speaker's bureau for Sucampo Pharmaceuticals, Takeda Pharmaceutical North America, Novartis, and Microbia.

SALT LAKE CITY – Narcotic bowel syndrome is a problem that physicians have been sweeping under the rug, and it may be growing in frequency, Dr. Douglas A. Drossman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Physicians have ignored this syndrome, since many are loathe to undertake the arduous task of weaning their patients from narcotics, said Dr. Drossman, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders.

But this reluctance is not necessary, because patients can be helped to break the “vicious cycle,” he said. There is a very effective protocol that can be used to withdraw patients from narcotics, using clonidine for the physical withdrawal symptoms and lorazepam for the anxiety, while switching them to an antidepressant for pain control.

This syndrome was first noted and described in the 1980s, but very little has been written about it, Dr. Drossman said. Since the 1980s, almost nothing has been published on the topic until recently, when Dr. Drossman and his colleagues Dr. David Grunkemeier, Dr. Joseph Cassara, and Ms. Christine Dalton published a paper (Clin. Gastroenterol. Hepatol. 2007;5:1126–39).

He has seen at least 100 patients with narcotic bowel syndrome in his clinic.

Typically, the patient with narcotic bowel syndrome was started on an opiate because of a functional bowel disorder, or after surgery, or even for an acute painful condition. The patient then developed chronic or intermittent colicky abdominal pain, often due to delayed motility.

At first, the narcotic helps this pain, but over time tachyphylaxis and hyperalgesia set in, rendering the narcotic less and less effective and making the patient dependent on ever-escalating doses.

Dr. Drossman likened the situation to using alcohol to treat a patient with delirium tremens. The alcohol relieves the acute symptoms, but it also perpetuates the cycle.

Dr. Drossman, a gastroenterologist who is trained in psychosomatic medicine, said narcotic bowel syndrome often gets pushed to the background. Narcotics are prescribed because that's what the patient wants, and clinics and hospitals pressure physicians to move patients through the system fast.

The doctors do not have the time or the motivation to address such a complex problem in a medical system that dictates quick processing of patients, Dr. Drossman said.

Narcotic bowel syndrome is probably a U.S. phenomenon, since narcotics are not used as frequently in the rest of the world. About 80% of the world's medical use of narcotics occurs in the United States, and physicians here are using opiates more and more, he said.

According to the protocol Dr. Drossman recommends, physicians who want to detoxify a patient should start with a tricyclic antidepressant or a serotonin-noradrenergic inhibitor, which is begun about 2 days before the withdrawal is initiated. Of the tricyclics, desipramine or nortriptyline are better than imipramine or amitriptyline because they have fewer side effects, he said.

A low dose is used for pain control, for example 50 mg per day of desipramine taken at bedtime, which is titrated up to 150 mg per day.

One day before narcotic withdrawal begins, lorazepam is started in order to ease anxiety, at a dose of 1 mg every 6–8 hours, continued throughout the entire withdrawal.

The narcotic can be withdrawn at a rate of 10%–33% per day, meaning the detoxification can take anywhere from 3 to 10 days.

On the second or third day of the withdrawal, clonidine is begun to treat the sympathetic-related symptoms, such as muscle pains and chills. Both the lorazepam and the clonidine can be tapered and discontinued once the withdrawal is complete.

If the patient is constipated, he or she can be treated with polyethylene glycol. The antidepressant is continued indefinitely, as needed, for pain control.

Dr. Drossman is on the speaker's bureau for Sucampo Pharmaceuticals, Takeda Pharmaceutical North America, Novartis, and Microbia.

SALT LAKE CITY – Narcotic bowel syndrome is a problem that physicians have been sweeping under the rug, and it may be growing in frequency, Dr. Douglas A. Drossman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Physicians have ignored this syndrome, since many are loathe to undertake the arduous task of weaning their patients from narcotics, said Dr. Drossman, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders.

But this reluctance is not necessary, because patients can be helped to break the “vicious cycle,” he said. There is a very effective protocol that can be used to withdraw patients from narcotics, using clonidine for the physical withdrawal symptoms and lorazepam for the anxiety, while switching them to an antidepressant for pain control.

This syndrome was first noted and described in the 1980s, but very little has been written about it, Dr. Drossman said. Since the 1980s, almost nothing has been published on the topic until recently, when Dr. Drossman and his colleagues Dr. David Grunkemeier, Dr. Joseph Cassara, and Ms. Christine Dalton published a paper (Clin. Gastroenterol. Hepatol. 2007;5:1126–39).

He has seen at least 100 patients with narcotic bowel syndrome in his clinic.

Typically, the patient with narcotic bowel syndrome was started on an opiate because of a functional bowel disorder, or after surgery, or even for an acute painful condition. The patient then developed chronic or intermittent colicky abdominal pain, often due to delayed motility.

At first, the narcotic helps this pain, but over time tachyphylaxis and hyperalgesia set in, rendering the narcotic less and less effective and making the patient dependent on ever-escalating doses.

Dr. Drossman likened the situation to using alcohol to treat a patient with delirium tremens. The alcohol relieves the acute symptoms, but it also perpetuates the cycle.

Dr. Drossman, a gastroenterologist who is trained in psychosomatic medicine, said narcotic bowel syndrome often gets pushed to the background. Narcotics are prescribed because that's what the patient wants, and clinics and hospitals pressure physicians to move patients through the system fast.

The doctors do not have the time or the motivation to address such a complex problem in a medical system that dictates quick processing of patients, Dr. Drossman said.

Narcotic bowel syndrome is probably a U.S. phenomenon, since narcotics are not used as frequently in the rest of the world. About 80% of the world's medical use of narcotics occurs in the United States, and physicians here are using opiates more and more, he said.

According to the protocol Dr. Drossman recommends, physicians who want to detoxify a patient should start with a tricyclic antidepressant or a serotonin-noradrenergic inhibitor, which is begun about 2 days before the withdrawal is initiated. Of the tricyclics, desipramine or nortriptyline are better than imipramine or amitriptyline because they have fewer side effects, he said.

A low dose is used for pain control, for example 50 mg per day of desipramine taken at bedtime, which is titrated up to 150 mg per day.

One day before narcotic withdrawal begins, lorazepam is started in order to ease anxiety, at a dose of 1 mg every 6–8 hours, continued throughout the entire withdrawal.

The narcotic can be withdrawn at a rate of 10%–33% per day, meaning the detoxification can take anywhere from 3 to 10 days.

On the second or third day of the withdrawal, clonidine is begun to treat the sympathetic-related symptoms, such as muscle pains and chills. Both the lorazepam and the clonidine can be tapered and discontinued once the withdrawal is complete.

If the patient is constipated, he or she can be treated with polyethylene glycol. The antidepressant is continued indefinitely, as needed, for pain control.

Dr. Drossman is on the speaker's bureau for Sucampo Pharmaceuticals, Takeda Pharmaceutical North America, Novartis, and Microbia.

Iatrogenic events occur quite frequently in the care of high-risk neonates, according to a study from France that found 116 of 388 patients admitted to a neonatal unit experienced an event.

Twenty-nine percent of the 267 events were considered severe, and 34% were judged to have been preventable.

An event was defined as something that potentially compromised a patient's safety. A severe event was defined as any event that resulted in disability, death, or an extended hospital stay.

"Our study has shown that a substantial proportion of neonates admitted to hospital had iatrogenic events, a significant proportion of which were preventable," wrote Dr. Isabelle Ligi of the division of neonatology of La Conception Hospital in Marseille, and her colleagues (Lancet 2008;371:404–10).

The study showed an incidence rate of 26 events per 1,000 patient days. Fifty-six of the 116 patients who experienced an event experienced more than one. Two patients died following an iatrogenic event, although in neither case was that event considered preventable.

The study was a test of an anonymous, iatrogenic-event reporting system designed by the hospital's neonatology division, and it considered the events reported among all admissions between Jan. 1, 2005, and Sept. 1, 2005.

The study findings suggest that iatrogenic events in hospitalized neonates may be less often preventable than those that occur to adults and older children, Dr. Ligi and her associates said. It is estimated that 40%–60% of iatrogenic adverse events in adults and children are preventable. In this study, only 34% were judged preventable, and only 21 of 78 events (27%) that were considered severe were judged preventable.

The investigators also reported that the major risk factors for an event included low gestational age and low birth weight, use of a central line, and mechanical ventilation.

Cutaneous injuries and nosocomial infections were the most common events recorded; nosocomial infections and respiratory iatrogenic events were the most severe, Dr. Ligi and her associates said.

Out of a total of 267 events recorded, 94 (35%) were cutaneous events and 62 (23%) were nosocomial infections. Forty-nine (79%) of the nosocomial infections were considered severe and nine of the 26 (35%) respiratory events were considered severe. Drug-related (34) events were common, but usually minor.

In a commentary published with the study, Dr. Gitte Larsen and Dr. Howard Parker said the study shows how efforts to reduce medical errors and other iatrogenic events need to be implemented locally (Lancet 2008;371:364–5).

Individual hospitals need to know what their specific errors are, and strategies developed nationally to reduce errors are likely to be inadequate, said Dr. Larsen and Dr. Parker of Primary Children's Medical Center, Salt Lake City, Utah.

Iatrogenic events occur quite frequently in the care of high-risk neonates, according to a study from France that found 116 of 388 patients admitted to a neonatal unit experienced an event.

Twenty-nine percent of the 267 events were considered severe, and 34% were judged to have been preventable.

An event was defined as something that potentially compromised a patient's safety. A severe event was defined as any event that resulted in disability, death, or an extended hospital stay.

"Our study has shown that a substantial proportion of neonates admitted to hospital had iatrogenic events, a significant proportion of which were preventable," wrote Dr. Isabelle Ligi of the division of neonatology of La Conception Hospital in Marseille, and her colleagues (Lancet 2008;371:404–10).

The study showed an incidence rate of 26 events per 1,000 patient days. Fifty-six of the 116 patients who experienced an event experienced more than one. Two patients died following an iatrogenic event, although in neither case was that event considered preventable.

The study was a test of an anonymous, iatrogenic-event reporting system designed by the hospital's neonatology division, and it considered the events reported among all admissions between Jan. 1, 2005, and Sept. 1, 2005.

The study findings suggest that iatrogenic events in hospitalized neonates may be less often preventable than those that occur to adults and older children, Dr. Ligi and her associates said. It is estimated that 40%–60% of iatrogenic adverse events in adults and children are preventable. In this study, only 34% were judged preventable, and only 21 of 78 events (27%) that were considered severe were judged preventable.

The investigators also reported that the major risk factors for an event included low gestational age and low birth weight, use of a central line, and mechanical ventilation.

Cutaneous injuries and nosocomial infections were the most common events recorded; nosocomial infections and respiratory iatrogenic events were the most severe, Dr. Ligi and her associates said.

Out of a total of 267 events recorded, 94 (35%) were cutaneous events and 62 (23%) were nosocomial infections. Forty-nine (79%) of the nosocomial infections were considered severe and nine of the 26 (35%) respiratory events were considered severe. Drug-related (34) events were common, but usually minor.

In a commentary published with the study, Dr. Gitte Larsen and Dr. Howard Parker said the study shows how efforts to reduce medical errors and other iatrogenic events need to be implemented locally (Lancet 2008;371:364–5).

Individual hospitals need to know what their specific errors are, and strategies developed nationally to reduce errors are likely to be inadequate, said Dr. Larsen and Dr. Parker of Primary Children's Medical Center, Salt Lake City, Utah.

Iatrogenic events occur quite frequently in the care of high-risk neonates, according to a study from France that found 116 of 388 patients admitted to a neonatal unit experienced an event.

Twenty-nine percent of the 267 events were considered severe, and 34% were judged to have been preventable.

An event was defined as something that potentially compromised a patient's safety. A severe event was defined as any event that resulted in disability, death, or an extended hospital stay.

"Our study has shown that a substantial proportion of neonates admitted to hospital had iatrogenic events, a significant proportion of which were preventable," wrote Dr. Isabelle Ligi of the division of neonatology of La Conception Hospital in Marseille, and her colleagues (Lancet 2008;371:404–10).

The study showed an incidence rate of 26 events per 1,000 patient days. Fifty-six of the 116 patients who experienced an event experienced more than one. Two patients died following an iatrogenic event, although in neither case was that event considered preventable.

The study was a test of an anonymous, iatrogenic-event reporting system designed by the hospital's neonatology division, and it considered the events reported among all admissions between Jan. 1, 2005, and Sept. 1, 2005.

The study findings suggest that iatrogenic events in hospitalized neonates may be less often preventable than those that occur to adults and older children, Dr. Ligi and her associates said. It is estimated that 40%–60% of iatrogenic adverse events in adults and children are preventable. In this study, only 34% were judged preventable, and only 21 of 78 events (27%) that were considered severe were judged preventable.

The investigators also reported that the major risk factors for an event included low gestational age and low birth weight, use of a central line, and mechanical ventilation.

Cutaneous injuries and nosocomial infections were the most common events recorded; nosocomial infections and respiratory iatrogenic events were the most severe, Dr. Ligi and her associates said.

Out of a total of 267 events recorded, 94 (35%) were cutaneous events and 62 (23%) were nosocomial infections. Forty-nine (79%) of the nosocomial infections were considered severe and nine of the 26 (35%) respiratory events were considered severe. Drug-related (34) events were common, but usually minor.

In a commentary published with the study, Dr. Gitte Larsen and Dr. Howard Parker said the study shows how efforts to reduce medical errors and other iatrogenic events need to be implemented locally (Lancet 2008;371:364–5).

Individual hospitals need to know what their specific errors are, and strategies developed nationally to reduce errors are likely to be inadequate, said Dr. Larsen and Dr. Parker of Primary Children's Medical Center, Salt Lake City, Utah.

LAS VEGAS — Dermatologists should tell their patients to be skeptical of "peptide" cosmeceuticals and to stick with proven agents, Dr. Kathy A. Fields said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Agents such as palmitoyl pentapeptide-3 have been shown to stimulate collagen production in a skin culture, but as with so many cosmeceutical products, none of the peptides has been proven to be effective in a published clinical trial or has any compelling scientific data, said Dr. Fields, a dermatologist in San Francisco who is a coinventor of Proactiv Solution, the popular acne treatment, and has her own line of cosmeceuticals, Rodan + Fields.

The peptides in cosmeceuticals may or may not penetrate the stratum corneum to any great degree, and they need to reach the dermis to be taken up by cells to have their effects.

"They don't last long," she said of the cosmeceutical peptides. "When you apply them on the skin, they go away rapidly. So they either don't penetrate or if they do, they may not have enough time or enough concentration to get to the target organs to make collagen."

Peptide-containing cosmeceuticals can also cost a lot, Dr. Fields said. StriVectin-SD, for example, costs about $135 for a 6-ounce tube when purchased from the manufacturer, and it contains palmitoyl pentapeptide as a reported active ingredient.

There is also little need for a patient interested in a skin rejuvenating regimen to use a peptide product because there are proven agents such as α-hydroxy acids and salicylic acid, and retinoids such as tretinoin and retinol.

Those are the agents she recommends to patients. "I love the old technology," she said.

If a patient does not tolerate a retinoid or one of the other older agents, she tells them to just use it twice a week to get started, rather than switch to a product that may be dubious. The patient can probably work up to using it more often.

LAS VEGAS — Dermatologists should tell their patients to be skeptical of "peptide" cosmeceuticals and to stick with proven agents, Dr. Kathy A. Fields said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Agents such as palmitoyl pentapeptide-3 have been shown to stimulate collagen production in a skin culture, but as with so many cosmeceutical products, none of the peptides has been proven to be effective in a published clinical trial or has any compelling scientific data, said Dr. Fields, a dermatologist in San Francisco who is a coinventor of Proactiv Solution, the popular acne treatment, and has her own line of cosmeceuticals, Rodan + Fields.

The peptides in cosmeceuticals may or may not penetrate the stratum corneum to any great degree, and they need to reach the dermis to be taken up by cells to have their effects.

"They don't last long," she said of the cosmeceutical peptides. "When you apply them on the skin, they go away rapidly. So they either don't penetrate or if they do, they may not have enough time or enough concentration to get to the target organs to make collagen."

Peptide-containing cosmeceuticals can also cost a lot, Dr. Fields said. StriVectin-SD, for example, costs about $135 for a 6-ounce tube when purchased from the manufacturer, and it contains palmitoyl pentapeptide as a reported active ingredient.

There is also little need for a patient interested in a skin rejuvenating regimen to use a peptide product because there are proven agents such as α-hydroxy acids and salicylic acid, and retinoids such as tretinoin and retinol.

Those are the agents she recommends to patients. "I love the old technology," she said.

If a patient does not tolerate a retinoid or one of the other older agents, she tells them to just use it twice a week to get started, rather than switch to a product that may be dubious. The patient can probably work up to using it more often.

LAS VEGAS — Dermatologists should tell their patients to be skeptical of "peptide" cosmeceuticals and to stick with proven agents, Dr. Kathy A. Fields said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Agents such as palmitoyl pentapeptide-3 have been shown to stimulate collagen production in a skin culture, but as with so many cosmeceutical products, none of the peptides has been proven to be effective in a published clinical trial or has any compelling scientific data, said Dr. Fields, a dermatologist in San Francisco who is a coinventor of Proactiv Solution, the popular acne treatment, and has her own line of cosmeceuticals, Rodan + Fields.

The peptides in cosmeceuticals may or may not penetrate the stratum corneum to any great degree, and they need to reach the dermis to be taken up by cells to have their effects.

"They don't last long," she said of the cosmeceutical peptides. "When you apply them on the skin, they go away rapidly. So they either don't penetrate or if they do, they may not have enough time or enough concentration to get to the target organs to make collagen."

Peptide-containing cosmeceuticals can also cost a lot, Dr. Fields said. StriVectin-SD, for example, costs about $135 for a 6-ounce tube when purchased from the manufacturer, and it contains palmitoyl pentapeptide as a reported active ingredient.

There is also little need for a patient interested in a skin rejuvenating regimen to use a peptide product because there are proven agents such as α-hydroxy acids and salicylic acid, and retinoids such as tretinoin and retinol.

Those are the agents she recommends to patients. "I love the old technology," she said.

If a patient does not tolerate a retinoid or one of the other older agents, she tells them to just use it twice a week to get started, rather than switch to a product that may be dubious. The patient can probably work up to using it more often.

Recent months have had a raft of bad news about injection lipolysis. Two prominent medical spas whose business was providing the popular treatments abruptly closed their doors, leaving patients in the lurch. Then, the Kansas Board of Healing Arts took action to strictly control the practice, a few months after trying to ban it.

Dr. Joel Schlessinger, immediate past president of the American Society of Cosmetic Dermatology and Aesthetic Surgery, warned the society that lipolysis might be neither effective nor safe, and he urged society members not to practice lipolysis until the ingredients used in the injections become Food and Drug Administration approved.

Recent news articles about this increasingly practiced treatment, popularly known as Lipodissolve, have tended to focus on individuals who complain of having permanent nodules or indentations from the procedure or who tell of rushing to the emergency department.

On the Web site www.realself.com

The Web site reported that an analysis of the IP addresses of the reviewers showed that many of the positive reviews came from one of the two now-defunct companies, Go Fig Inc., without the authors identifying themselves, and some came from MedSculpt (both companies are now out of business).

But while agreeing that better regulation might be a good idea, physicians who perform the procedure think that their experience and studies suggest the risks of complications are quite low and the results, in properly selected patients, generally good.

Support for Mesotherapy

"Injection lipolysis is not without risk, but it is pretty darn safe," said Dr. Thomas Wright, an internist who has a cosmetic practice in suburban St. Louis. He has been collecting reports of cases and complications from members of the American Society of Nonsurgical Aesthetics.

In reviewing about 200,000 treatment cases either reported to him or that he has sought out, he has found only 2 definite cases in which there was a serious complication. Both were cases of skin ulceration at or near sites of injection that needed skin graft repair. Overall, he said that he has found about 20 cases of skin breakdown or a pigment change, though some of those were extremely small, a millimeter in size.

He reported having recorded no other confirmed complications.

"We've been using injection lipolysis in my clinic for 2 years now and getting excellent results," said Dr. Charles E. Crutchfield III, a dermatologist who practices in Minneapolis.

Dr. Crutchfield said the only serious complications he has seen or heard of are cases of skin ulceration. It is thought ulceration happens because of injections placed too superficially.

Dr. Crutchfield is a member of the medical advisory board of the American Society of Aesthetic Lipodissolve, a professional organization that owns a copyright on the term Lipodissolve and provides training in the procedure. Dr. Wright is also a medical advisory board member with the group.

Reports of Complications Conflict

Andrew Noel, a photographer from Las Vegas, had treatments at a Go Fig spa, and he said that 4 months after his last treatment, he still has welts "the size of 50-cent pieces" on his abdomen where he received the injections.

"My tummy is disfigured and I am steaming mad," he said.

Dr. Alastair Carruthers, a dermatologist in Vancouver, B.C., has seen two patients who had complications presumed to be from Lipodissolve treatments, the first in a woman who was injected in her lower eyelids and the second in a woman injected in her thighs.

The second woman developed significant ulceration that caused scarring, Dr. Carruthers said.

Dr. Elizabeth Tanzi, a dermatologist in practice in Washington, has seen four patients with complications from Lipodissolve treatment, two with "an unnatural firmness" that resolved only slowly, one with a vascular pattern over the treated area that lasted for a year and required laser treatment, and another patient who had a draining nodule.

But surveys, like Dr. Wright's, of physicians who practice injection lipolysis suggest that the procedure—while sometimes causing discomfort and leaving temporary nodules in treated areas that resolve over time—only rarely has complications.

And another survey of 75 practitioners reported that among 17,376 patients treated there were no hospitalizations, no deaths, and no cases of skin necrosis (Aesthetic Surg. J. 2006;26:575–85). Moreover, less than 1% of patients reported to their physicians pain that lasted beyond 2 weeks, and the most common complaint of patients was a less than desired result, reported for 12% of patients. Nineteen of the practitioners reported having seen hyperpigmentation, but in the majority of cases this resolved within 3 months.

Safety Concerns

Another of the concerns with lipolysis treatment is whether there might be long-term effects from phosphatidylcholine or sodium deoxycholate, or acute problems from exposure to those ingredients or from the release of so much fat at once.

The substances are both naturally present in the human body already, and used the way they are to reduce fat, have only "relatively benign, localized effects," said Dr. Adam Rotunda, a physician who now works as a medical director of research and development at Allergan Inc., but who conducted research on injection lipolysis as a dermatology resident at the University of California, Los Angeles.

Dr. Rotunda has a patent for a formulation of sodium deoxycholate (licensed to Kythera Biopharmaceuticals Inc.) alone for injection lipolysis, which he claims might be as effective as the phosphatidylcholine/sodium deoxycholate combination. That formulation is at present in clinical trials. Dr. Rotunda has no financial interest in the product, though he has received consulting fees from Kythera. The licensing fees are paid to the University of California, Los Angeles, he disclosed.

A Flawed Business Plan?

Dr. Wright said he is very familiar with one of the now-defunct companies, Fig, which was based in the St. Louis area. He is not only well acquainted with the former principals in the company, but he has treated about 30 former Fig patients. And he suggests that many of the complaints and complications being reported about injection lipolysis come from Fig clients, who were guaranteed results or a refund.

The company often had no physician onsite at its locations and many sometimes used doses too high and treated inappropriate patients. Dr. Wright recalled one patient who went to a Fig location every month for a year to be treated and never once saw a physician.

"The company was selling to inappropriate candidates and overselling," he said.

Many Fig patients that Dr. Wright said he treated were extremely overweight, and the proper candidate for lipolysis is one who is not overweight but simply has a localized area with a small amount of fat they would like to be rid of. Fig—which had 18 locations in various states—ceased its operations in December and filed for chapter 11 bankruptcy in January. The other prominent company that recently closed was MedSculpt, a firm with locations in Rockville, Md., and Fairfax, Va., which went into receivership in January.

Officials from both companies were unavailable for comment, and physicians connected with the companies either declined to comment or did not return calls and e-mails. However, in statements, Fig representatives said their investors pulled funding, and blamed the situation in part on a downturn in customers and bad press. MedSculpt needed a cash infusion and had investors lined up, but when Fig closed those investors balked, the representatives claim.

Recent Studies

Two studies have looked at whether the treatment has any identifiable systemic effects, and neither found any, said Dr. Rotunda. "We don't have the quality of data we need, but what we do have is pretty reassuring."

Brazilian investigators treated 30 patients with a series of four sessions of abdominal injections of sodium deoxycholate and looked at the local and systemic effects. At different time periods—ranging from 2 hours after an injection to 12 weeks—they measured lipids and kidney and liver function and found no significant changes (Dermatol. Surg. 2007;33:178–89).

In his own work, Dr. Rotunda has found that injecting phosphatidylcholine and sodium deoxycholate can produce changes in muscle architecture but the substances have to be injected directly into the muscles (Dermatol. Surg. 2004;30:1001–8).

Patients can experience nausea from the procedure, but that appears to be a cholinergic effect that occurs when too high a dose is used, he said.

Currently the evidence of the efficacy of injection lipolysis is anecdotal. But in November, a clinical trial of the combination solution got underway, sponsored by the Aesthetic Surgery Education and Research Foundation, run by Dr. V. Leroy Young, a former professor of plastic and reconstructive surgery at Washington University, St. Louis, who is now in private practice. The trial will enroll 20 subjects, who will be followed for 46 weeks.

In the meantime, both Dr. Crutchfield and Dr. Wright said they would have no problem if the FDA or some other agency came to regulate lipolysis procedures or the compounded ingredients used.

But Dr. Crutchfield also noted that injection lipolysis is not the first cosmetic product to be used off-label, and he cited Botox as an example. Botox was used cosmetically before its approval and currently is used in locations where it is not approved.

"If you are going to talk about this lacking FDA approval as a reason physicians should not be doing it, you are going to have to point the finger at everybody who does Botox," Dr. Crutchfield said.

Lipolysis has grown in popularity, while at the same time, a number of groups have expressed concern that it has no Food and Drug Administration approval, and have issued warnings about the procedure, saying there is no good clinical trial data to affirm benefit from the procedure and safety is not established.

Lipolysis may be neither safe nor effective, and shouldn't be used until approved by the FDA. DR. SCHLESSINGER

Ihave seen two patients who have had complications presumed to be from Lipodissolve treatments. DR. CARRUTHERS

Recent months have had a raft of bad news about injection lipolysis. Two prominent medical spas whose business was providing the popular treatments abruptly closed their doors, leaving patients in the lurch. Then, the Kansas Board of Healing Arts took action to strictly control the practice, a few months after trying to ban it.

Dr. Joel Schlessinger, immediate past president of the American Society of Cosmetic Dermatology and Aesthetic Surgery, warned the society that lipolysis might be neither effective nor safe, and he urged society members not to practice lipolysis until the ingredients used in the injections become Food and Drug Administration approved.

Recent news articles about this increasingly practiced treatment, popularly known as Lipodissolve, have tended to focus on individuals who complain of having permanent nodules or indentations from the procedure or who tell of rushing to the emergency department.

On the Web site www.realself.com

The Web site reported that an analysis of the IP addresses of the reviewers showed that many of the positive reviews came from one of the two now-defunct companies, Go Fig Inc., without the authors identifying themselves, and some came from MedSculpt (both companies are now out of business).

But while agreeing that better regulation might be a good idea, physicians who perform the procedure think that their experience and studies suggest the risks of complications are quite low and the results, in properly selected patients, generally good.

Support for Mesotherapy

"Injection lipolysis is not without risk, but it is pretty darn safe," said Dr. Thomas Wright, an internist who has a cosmetic practice in suburban St. Louis. He has been collecting reports of cases and complications from members of the American Society of Nonsurgical Aesthetics.

In reviewing about 200,000 treatment cases either reported to him or that he has sought out, he has found only 2 definite cases in which there was a serious complication. Both were cases of skin ulceration at or near sites of injection that needed skin graft repair. Overall, he said that he has found about 20 cases of skin breakdown or a pigment change, though some of those were extremely small, a millimeter in size.

He reported having recorded no other confirmed complications.

"We've been using injection lipolysis in my clinic for 2 years now and getting excellent results," said Dr. Charles E. Crutchfield III, a dermatologist who practices in Minneapolis.

Dr. Crutchfield said the only serious complications he has seen or heard of are cases of skin ulceration. It is thought ulceration happens because of injections placed too superficially.

Dr. Crutchfield is a member of the medical advisory board of the American Society of Aesthetic Lipodissolve, a professional organization that owns a copyright on the term Lipodissolve and provides training in the procedure. Dr. Wright is also a medical advisory board member with the group.

Reports of Complications Conflict

Andrew Noel, a photographer from Las Vegas, had treatments at a Go Fig spa, and he said that 4 months after his last treatment, he still has welts "the size of 50-cent pieces" on his abdomen where he received the injections.

"My tummy is disfigured and I am steaming mad," he said.

Dr. Alastair Carruthers, a dermatologist in Vancouver, B.C., has seen two patients who had complications presumed to be from Lipodissolve treatments, the first in a woman who was injected in her lower eyelids and the second in a woman injected in her thighs.

The second woman developed significant ulceration that caused scarring, Dr. Carruthers said.

Dr. Elizabeth Tanzi, a dermatologist in practice in Washington, has seen four patients with complications from Lipodissolve treatment, two with "an unnatural firmness" that resolved only slowly, one with a vascular pattern over the treated area that lasted for a year and required laser treatment, and another patient who had a draining nodule.

But surveys, like Dr. Wright's, of physicians who practice injection lipolysis suggest that the procedure—while sometimes causing discomfort and leaving temporary nodules in treated areas that resolve over time—only rarely has complications.

And another survey of 75 practitioners reported that among 17,376 patients treated there were no hospitalizations, no deaths, and no cases of skin necrosis (Aesthetic Surg. J. 2006;26:575–85). Moreover, less than 1% of patients reported to their physicians pain that lasted beyond 2 weeks, and the most common complaint of patients was a less than desired result, reported for 12% of patients. Nineteen of the practitioners reported having seen hyperpigmentation, but in the majority of cases this resolved within 3 months.

Safety Concerns

Another of the concerns with lipolysis treatment is whether there might be long-term effects from phosphatidylcholine or sodium deoxycholate, or acute problems from exposure to those ingredients or from the release of so much fat at once.

The substances are both naturally present in the human body already, and used the way they are to reduce fat, have only "relatively benign, localized effects," said Dr. Adam Rotunda, a physician who now works as a medical director of research and development at Allergan Inc., but who conducted research on injection lipolysis as a dermatology resident at the University of California, Los Angeles.

Dr. Rotunda has a patent for a formulation of sodium deoxycholate (licensed to Kythera Biopharmaceuticals Inc.) alone for injection lipolysis, which he claims might be as effective as the phosphatidylcholine/sodium deoxycholate combination. That formulation is at present in clinical trials. Dr. Rotunda has no financial interest in the product, though he has received consulting fees from Kythera. The licensing fees are paid to the University of California, Los Angeles, he disclosed.

A Flawed Business Plan?

Dr. Wright said he is very familiar with one of the now-defunct companies, Fig, which was based in the St. Louis area. He is not only well acquainted with the former principals in the company, but he has treated about 30 former Fig patients. And he suggests that many of the complaints and complications being reported about injection lipolysis come from Fig clients, who were guaranteed results or a refund.

The company often had no physician onsite at its locations and many sometimes used doses too high and treated inappropriate patients. Dr. Wright recalled one patient who went to a Fig location every month for a year to be treated and never once saw a physician.

"The company was selling to inappropriate candidates and overselling," he said.

Many Fig patients that Dr. Wright said he treated were extremely overweight, and the proper candidate for lipolysis is one who is not overweight but simply has a localized area with a small amount of fat they would like to be rid of. Fig—which had 18 locations in various states—ceased its operations in December and filed for chapter 11 bankruptcy in January. The other prominent company that recently closed was MedSculpt, a firm with locations in Rockville, Md., and Fairfax, Va., which went into receivership in January.

Officials from both companies were unavailable for comment, and physicians connected with the companies either declined to comment or did not return calls and e-mails. However, in statements, Fig representatives said their investors pulled funding, and blamed the situation in part on a downturn in customers and bad press. MedSculpt needed a cash infusion and had investors lined up, but when Fig closed those investors balked, the representatives claim.

Recent Studies

Two studies have looked at whether the treatment has any identifiable systemic effects, and neither found any, said Dr. Rotunda. "We don't have the quality of data we need, but what we do have is pretty reassuring."

Brazilian investigators treated 30 patients with a series of four sessions of abdominal injections of sodium deoxycholate and looked at the local and systemic effects. At different time periods—ranging from 2 hours after an injection to 12 weeks—they measured lipids and kidney and liver function and found no significant changes (Dermatol. Surg. 2007;33:178–89).

In his own work, Dr. Rotunda has found that injecting phosphatidylcholine and sodium deoxycholate can produce changes in muscle architecture but the substances have to be injected directly into the muscles (Dermatol. Surg. 2004;30:1001–8).

Patients can experience nausea from the procedure, but that appears to be a cholinergic effect that occurs when too high a dose is used, he said.

Currently the evidence of the efficacy of injection lipolysis is anecdotal. But in November, a clinical trial of the combination solution got underway, sponsored by the Aesthetic Surgery Education and Research Foundation, run by Dr. V. Leroy Young, a former professor of plastic and reconstructive surgery at Washington University, St. Louis, who is now in private practice. The trial will enroll 20 subjects, who will be followed for 46 weeks.

In the meantime, both Dr. Crutchfield and Dr. Wright said they would have no problem if the FDA or some other agency came to regulate lipolysis procedures or the compounded ingredients used.

But Dr. Crutchfield also noted that injection lipolysis is not the first cosmetic product to be used off-label, and he cited Botox as an example. Botox was used cosmetically before its approval and currently is used in locations where it is not approved.

"If you are going to talk about this lacking FDA approval as a reason physicians should not be doing it, you are going to have to point the finger at everybody who does Botox," Dr. Crutchfield said.

Lipolysis has grown in popularity, while at the same time, a number of groups have expressed concern that it has no Food and Drug Administration approval, and have issued warnings about the procedure, saying there is no good clinical trial data to affirm benefit from the procedure and safety is not established.

Lipolysis may be neither safe nor effective, and shouldn't be used until approved by the FDA. DR. SCHLESSINGER

Ihave seen two patients who have had complications presumed to be from Lipodissolve treatments. DR. CARRUTHERS

Recent months have had a raft of bad news about injection lipolysis. Two prominent medical spas whose business was providing the popular treatments abruptly closed their doors, leaving patients in the lurch. Then, the Kansas Board of Healing Arts took action to strictly control the practice, a few months after trying to ban it.

Dr. Joel Schlessinger, immediate past president of the American Society of Cosmetic Dermatology and Aesthetic Surgery, warned the society that lipolysis might be neither effective nor safe, and he urged society members not to practice lipolysis until the ingredients used in the injections become Food and Drug Administration approved.

Recent news articles about this increasingly practiced treatment, popularly known as Lipodissolve, have tended to focus on individuals who complain of having permanent nodules or indentations from the procedure or who tell of rushing to the emergency department.

On the Web site www.realself.com

The Web site reported that an analysis of the IP addresses of the reviewers showed that many of the positive reviews came from one of the two now-defunct companies, Go Fig Inc., without the authors identifying themselves, and some came from MedSculpt (both companies are now out of business).

But while agreeing that better regulation might be a good idea, physicians who perform the procedure think that their experience and studies suggest the risks of complications are quite low and the results, in properly selected patients, generally good.

Support for Mesotherapy

"Injection lipolysis is not without risk, but it is pretty darn safe," said Dr. Thomas Wright, an internist who has a cosmetic practice in suburban St. Louis. He has been collecting reports of cases and complications from members of the American Society of Nonsurgical Aesthetics.

In reviewing about 200,000 treatment cases either reported to him or that he has sought out, he has found only 2 definite cases in which there was a serious complication. Both were cases of skin ulceration at or near sites of injection that needed skin graft repair. Overall, he said that he has found about 20 cases of skin breakdown or a pigment change, though some of those were extremely small, a millimeter in size.

He reported having recorded no other confirmed complications.

"We've been using injection lipolysis in my clinic for 2 years now and getting excellent results," said Dr. Charles E. Crutchfield III, a dermatologist who practices in Minneapolis.

Dr. Crutchfield said the only serious complications he has seen or heard of are cases of skin ulceration. It is thought ulceration happens because of injections placed too superficially.

Dr. Crutchfield is a member of the medical advisory board of the American Society of Aesthetic Lipodissolve, a professional organization that owns a copyright on the term Lipodissolve and provides training in the procedure. Dr. Wright is also a medical advisory board member with the group.

Reports of Complications Conflict

Andrew Noel, a photographer from Las Vegas, had treatments at a Go Fig spa, and he said that 4 months after his last treatment, he still has welts "the size of 50-cent pieces" on his abdomen where he received the injections.

"My tummy is disfigured and I am steaming mad," he said.

Dr. Alastair Carruthers, a dermatologist in Vancouver, B.C., has seen two patients who had complications presumed to be from Lipodissolve treatments, the first in a woman who was injected in her lower eyelids and the second in a woman injected in her thighs.

The second woman developed significant ulceration that caused scarring, Dr. Carruthers said.

Dr. Elizabeth Tanzi, a dermatologist in practice in Washington, has seen four patients with complications from Lipodissolve treatment, two with "an unnatural firmness" that resolved only slowly, one with a vascular pattern over the treated area that lasted for a year and required laser treatment, and another patient who had a draining nodule.

But surveys, like Dr. Wright's, of physicians who practice injection lipolysis suggest that the procedure—while sometimes causing discomfort and leaving temporary nodules in treated areas that resolve over time—only rarely has complications.

And another survey of 75 practitioners reported that among 17,376 patients treated there were no hospitalizations, no deaths, and no cases of skin necrosis (Aesthetic Surg. J. 2006;26:575–85). Moreover, less than 1% of patients reported to their physicians pain that lasted beyond 2 weeks, and the most common complaint of patients was a less than desired result, reported for 12% of patients. Nineteen of the practitioners reported having seen hyperpigmentation, but in the majority of cases this resolved within 3 months.

Safety Concerns

Another of the concerns with lipolysis treatment is whether there might be long-term effects from phosphatidylcholine or sodium deoxycholate, or acute problems from exposure to those ingredients or from the release of so much fat at once.

The substances are both naturally present in the human body already, and used the way they are to reduce fat, have only "relatively benign, localized effects," said Dr. Adam Rotunda, a physician who now works as a medical director of research and development at Allergan Inc., but who conducted research on injection lipolysis as a dermatology resident at the University of California, Los Angeles.

Dr. Rotunda has a patent for a formulation of sodium deoxycholate (licensed to Kythera Biopharmaceuticals Inc.) alone for injection lipolysis, which he claims might be as effective as the phosphatidylcholine/sodium deoxycholate combination. That formulation is at present in clinical trials. Dr. Rotunda has no financial interest in the product, though he has received consulting fees from Kythera. The licensing fees are paid to the University of California, Los Angeles, he disclosed.

A Flawed Business Plan?

Dr. Wright said he is very familiar with one of the now-defunct companies, Fig, which was based in the St. Louis area. He is not only well acquainted with the former principals in the company, but he has treated about 30 former Fig patients. And he suggests that many of the complaints and complications being reported about injection lipolysis come from Fig clients, who were guaranteed results or a refund.

The company often had no physician onsite at its locations and many sometimes used doses too high and treated inappropriate patients. Dr. Wright recalled one patient who went to a Fig location every month for a year to be treated and never once saw a physician.

"The company was selling to inappropriate candidates and overselling," he said.

Many Fig patients that Dr. Wright said he treated were extremely overweight, and the proper candidate for lipolysis is one who is not overweight but simply has a localized area with a small amount of fat they would like to be rid of. Fig—which had 18 locations in various states—ceased its operations in December and filed for chapter 11 bankruptcy in January. The other prominent company that recently closed was MedSculpt, a firm with locations in Rockville, Md., and Fairfax, Va., which went into receivership in January.

Officials from both companies were unavailable for comment, and physicians connected with the companies either declined to comment or did not return calls and e-mails. However, in statements, Fig representatives said their investors pulled funding, and blamed the situation in part on a downturn in customers and bad press. MedSculpt needed a cash infusion and had investors lined up, but when Fig closed those investors balked, the representatives claim.

Recent Studies

Two studies have looked at whether the treatment has any identifiable systemic effects, and neither found any, said Dr. Rotunda. "We don't have the quality of data we need, but what we do have is pretty reassuring."

Brazilian investigators treated 30 patients with a series of four sessions of abdominal injections of sodium deoxycholate and looked at the local and systemic effects. At different time periods—ranging from 2 hours after an injection to 12 weeks—they measured lipids and kidney and liver function and found no significant changes (Dermatol. Surg. 2007;33:178–89).

In his own work, Dr. Rotunda has found that injecting phosphatidylcholine and sodium deoxycholate can produce changes in muscle architecture but the substances have to be injected directly into the muscles (Dermatol. Surg. 2004;30:1001–8).

Patients can experience nausea from the procedure, but that appears to be a cholinergic effect that occurs when too high a dose is used, he said.

Currently the evidence of the efficacy of injection lipolysis is anecdotal. But in November, a clinical trial of the combination solution got underway, sponsored by the Aesthetic Surgery Education and Research Foundation, run by Dr. V. Leroy Young, a former professor of plastic and reconstructive surgery at Washington University, St. Louis, who is now in private practice. The trial will enroll 20 subjects, who will be followed for 46 weeks.

In the meantime, both Dr. Crutchfield and Dr. Wright said they would have no problem if the FDA or some other agency came to regulate lipolysis procedures or the compounded ingredients used.

But Dr. Crutchfield also noted that injection lipolysis is not the first cosmetic product to be used off-label, and he cited Botox as an example. Botox was used cosmetically before its approval and currently is used in locations where it is not approved.

"If you are going to talk about this lacking FDA approval as a reason physicians should not be doing it, you are going to have to point the finger at everybody who does Botox," Dr. Crutchfield said.

Lipolysis has grown in popularity, while at the same time, a number of groups have expressed concern that it has no Food and Drug Administration approval, and have issued warnings about the procedure, saying there is no good clinical trial data to affirm benefit from the procedure and safety is not established.

Lipolysis may be neither safe nor effective, and shouldn't be used until approved by the FDA. DR. SCHLESSINGER

Ihave seen two patients who have had complications presumed to be from Lipodissolve treatments. DR. CARRUTHERS

LAS VEGAS — Porcine collagen crosslinked with D-ribose probably lasts as long or longer than does hyaluronic acid when used as a cosmetic filler for lips and nasolabial folds, Dr. Gary Monheit said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The product, Evolence (Dermicol-P35) manufactured by ColBar LifeScience Ltd. (Israel), is approved for use in Europe and Canada and is expected to be approved in the United States, according to Dr. Monheit, principal investigator in the U.S. trial. The company has submitted an approval application to the Food and Drug Administration.

The trial's split-face design compared Evolence injection with hyaluronic acid (Restylane) injection in the nasolabial folds of 149 patients. After 6 months, there was no significant difference in the mean amount of correction the patients had on either side, as judged by study observers using the Modified Fitzpatrick Wrinkle Scale score (Dermatol. Surg. 2007;33:S213–21). Dr. Monheit disclosed receiving supplies and financial support from ColBar.

The secret to Evolence's longevity is thought to be the high level of crosslinking between the individual collagen fibers in the material, he said. "Because of this extra crosslinking, this is a very stable product that lasts over a year, possibly 2 years."

At 1-year follow-up, 90% of the patients that received Evolence still had some degree of improvement, said Dr. Monheit of the University of Alabama, Tuscaloosa. Evolence has been found to last up to 2 years when implanted into rabbit ears.

Raw material for Evolence comes from the tendons of pigs. In the first step of processing, the pig collagen's natural crosslinking is broken down by pepsin into monomeric collagen. Then the telopeptide of each collagen strand is removed because that part is the most immunogenic.

Pig collagen is used by ColBar because it is probably less immunogenic than beef collagen, he said.

Once the telopeptides are removed the material is again crosslinked, but instead of using glutaraldehyde or some other potentially problematic chemical to create the crosslinking, ColBar uses D-ribose, Dr. Monheit said.

LAS VEGAS — Porcine collagen crosslinked with D-ribose probably lasts as long or longer than does hyaluronic acid when used as a cosmetic filler for lips and nasolabial folds, Dr. Gary Monheit said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The product, Evolence (Dermicol-P35) manufactured by ColBar LifeScience Ltd. (Israel), is approved for use in Europe and Canada and is expected to be approved in the United States, according to Dr. Monheit, principal investigator in the U.S. trial. The company has submitted an approval application to the Food and Drug Administration.

The trial's split-face design compared Evolence injection with hyaluronic acid (Restylane) injection in the nasolabial folds of 149 patients. After 6 months, there was no significant difference in the mean amount of correction the patients had on either side, as judged by study observers using the Modified Fitzpatrick Wrinkle Scale score (Dermatol. Surg. 2007;33:S213–21). Dr. Monheit disclosed receiving supplies and financial support from ColBar.

The secret to Evolence's longevity is thought to be the high level of crosslinking between the individual collagen fibers in the material, he said. "Because of this extra crosslinking, this is a very stable product that lasts over a year, possibly 2 years."

At 1-year follow-up, 90% of the patients that received Evolence still had some degree of improvement, said Dr. Monheit of the University of Alabama, Tuscaloosa. Evolence has been found to last up to 2 years when implanted into rabbit ears.

Raw material for Evolence comes from the tendons of pigs. In the first step of processing, the pig collagen's natural crosslinking is broken down by pepsin into monomeric collagen. Then the telopeptide of each collagen strand is removed because that part is the most immunogenic.

Pig collagen is used by ColBar because it is probably less immunogenic than beef collagen, he said.

Once the telopeptides are removed the material is again crosslinked, but instead of using glutaraldehyde or some other potentially problematic chemical to create the crosslinking, ColBar uses D-ribose, Dr. Monheit said.

LAS VEGAS — Porcine collagen crosslinked with D-ribose probably lasts as long or longer than does hyaluronic acid when used as a cosmetic filler for lips and nasolabial folds, Dr. Gary Monheit said at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The product, Evolence (Dermicol-P35) manufactured by ColBar LifeScience Ltd. (Israel), is approved for use in Europe and Canada and is expected to be approved in the United States, according to Dr. Monheit, principal investigator in the U.S. trial. The company has submitted an approval application to the Food and Drug Administration.

The trial's split-face design compared Evolence injection with hyaluronic acid (Restylane) injection in the nasolabial folds of 149 patients. After 6 months, there was no significant difference in the mean amount of correction the patients had on either side, as judged by study observers using the Modified Fitzpatrick Wrinkle Scale score (Dermatol. Surg. 2007;33:S213–21). Dr. Monheit disclosed receiving supplies and financial support from ColBar.

The secret to Evolence's longevity is thought to be the high level of crosslinking between the individual collagen fibers in the material, he said. "Because of this extra crosslinking, this is a very stable product that lasts over a year, possibly 2 years."

At 1-year follow-up, 90% of the patients that received Evolence still had some degree of improvement, said Dr. Monheit of the University of Alabama, Tuscaloosa. Evolence has been found to last up to 2 years when implanted into rabbit ears.

Raw material for Evolence comes from the tendons of pigs. In the first step of processing, the pig collagen's natural crosslinking is broken down by pepsin into monomeric collagen. Then the telopeptide of each collagen strand is removed because that part is the most immunogenic.

Pig collagen is used by ColBar because it is probably less immunogenic than beef collagen, he said.

Once the telopeptides are removed the material is again crosslinked, but instead of using glutaraldehyde or some other potentially problematic chemical to create the crosslinking, ColBar uses D-ribose, Dr. Monheit said.