Mary Ann Moon

Cases of dextromethorphan abuse reported to the California Poison Control System increased 10-fold in all age groups–and increased 15-fold in adolescents–between 1999 and 2004, said Jodi K. Bryner, Pharm.D., of the University of California, San Francisco, and her associates.

A similar national trend was noted during the same time frame in two databases that track nationwide drug abuse, the researchers reported (Arch. Pediatr. Adolesc. Med. 2006;160:1217–22).

Dextromethorphan is increasingly popular among adolescents because it is easily–and legally–available in over-the-counter cough and cold remedies, is relatively inexpensive, and lacks the stigma of drug abuse.

Dr. Bryner and her associates examined trends in dextromethorphan abuse in a review of all 1,382 cases reported to California's poison control system during the 6-year period. A total of 75% of all cases occurred in adolescents, and the abuse peaked at age 15–16 years.

Most cases resulted in minor (46%) or moderate (42%) outcomes. Minor outcomes included minimal symptoms such as drowsiness, GI effects, or sinus tachycardia, which resolved rapidly. Moderate outcomes included more pronounced, prolonged, or systemic symptoms such as agitation, disorientation, hallucinations, brief hypotension, and a single brief seizure.

Major outcomes such as life-threatening symptoms or those that caused significant residual disability occurred in seven cases and included respiratory depression or aspiration requiring intubation, cardiovascular compromise, and prolonged or multiple seizures. There were no fatalities.

The extent of dextromethorphan abuse is likely far greater than that reported here, because often only the severest cases are called in to the poison control system and because laboratory testing for the drug is not routinely available in most hospitals, Dr. Bryner and her associates said.

Cases of dextromethorphan abuse reported to the California Poison Control System increased 10-fold in all age groups–and increased 15-fold in adolescents–between 1999 and 2004, said Jodi K. Bryner, Pharm.D., of the University of California, San Francisco, and her associates.

A similar national trend was noted during the same time frame in two databases that track nationwide drug abuse, the researchers reported (Arch. Pediatr. Adolesc. Med. 2006;160:1217–22).

Dextromethorphan is increasingly popular among adolescents because it is easily–and legally–available in over-the-counter cough and cold remedies, is relatively inexpensive, and lacks the stigma of drug abuse.

Dr. Bryner and her associates examined trends in dextromethorphan abuse in a review of all 1,382 cases reported to California's poison control system during the 6-year period. A total of 75% of all cases occurred in adolescents, and the abuse peaked at age 15–16 years.

Most cases resulted in minor (46%) or moderate (42%) outcomes. Minor outcomes included minimal symptoms such as drowsiness, GI effects, or sinus tachycardia, which resolved rapidly. Moderate outcomes included more pronounced, prolonged, or systemic symptoms such as agitation, disorientation, hallucinations, brief hypotension, and a single brief seizure.

Major outcomes such as life-threatening symptoms or those that caused significant residual disability occurred in seven cases and included respiratory depression or aspiration requiring intubation, cardiovascular compromise, and prolonged or multiple seizures. There were no fatalities.

The extent of dextromethorphan abuse is likely far greater than that reported here, because often only the severest cases are called in to the poison control system and because laboratory testing for the drug is not routinely available in most hospitals, Dr. Bryner and her associates said.

Cases of dextromethorphan abuse reported to the California Poison Control System increased 10-fold in all age groups–and increased 15-fold in adolescents–between 1999 and 2004, said Jodi K. Bryner, Pharm.D., of the University of California, San Francisco, and her associates.

A similar national trend was noted during the same time frame in two databases that track nationwide drug abuse, the researchers reported (Arch. Pediatr. Adolesc. Med. 2006;160:1217–22).

Dextromethorphan is increasingly popular among adolescents because it is easily–and legally–available in over-the-counter cough and cold remedies, is relatively inexpensive, and lacks the stigma of drug abuse.

Dr. Bryner and her associates examined trends in dextromethorphan abuse in a review of all 1,382 cases reported to California's poison control system during the 6-year period. A total of 75% of all cases occurred in adolescents, and the abuse peaked at age 15–16 years.

Most cases resulted in minor (46%) or moderate (42%) outcomes. Minor outcomes included minimal symptoms such as drowsiness, GI effects, or sinus tachycardia, which resolved rapidly. Moderate outcomes included more pronounced, prolonged, or systemic symptoms such as agitation, disorientation, hallucinations, brief hypotension, and a single brief seizure.

Major outcomes such as life-threatening symptoms or those that caused significant residual disability occurred in seven cases and included respiratory depression or aspiration requiring intubation, cardiovascular compromise, and prolonged or multiple seizures. There were no fatalities.

The extent of dextromethorphan abuse is likely far greater than that reported here, because often only the severest cases are called in to the poison control system and because laboratory testing for the drug is not routinely available in most hospitals, Dr. Bryner and her associates said.

White marathon runners are at significantly higher risk of developing malignant melanoma than are white people of the same age who don't spend 40 or more hours per week training or competing outdoors, reported Dr. Christina M. Ambros-Rudolph and her associates at the Medical University of Graz (Austria).

Compared with an age-, sex-, and race-matched control population, marathon runners were found to have significantly more atypical melanocytic nevi and solar lentigines. Their referral rate for removal of lesions suggestive of nonmelanoma skin cancer also was significantly higher than that of control subjects.

Both the number of lesions and the rate of referral for surgical excision increased as the number of hours spent training outdoors increased, the researchers said (Arch. Dermatol. 2006;142:1471–4).

Physicians should alert patients who are runners to “the crucial role of UV radiation in the development of malignant melanoma and nonmalignant skin cancers. In particular, they should be advised to reduce UV exposure during exercising by choosing training and competition schedules with low sun exposure, wearing adequate clothing, and regularly using water-resistant sunscreens,” Dr. Ambros-Rudolph and her associates said.

They became concerned about malignant melanoma incidence among runners when they observed eight cases of the disease in marathoners treated in their dermatology department over the past decade. The researchers are themselves “enthusiastic runners,” and two are regular marathoners, they noted.

In all eight cases, melanomas developed in areas that were uncovered or only partially covered by clothing—the upper back, lower thigh, and calf—and all but one were associated with an atypical or congenital melanocytic nevus.

To study the issue, the investigators assessed 210 white marathon runners (166 men and 44 women) aged 19–71 years and 210 white age- and sex-matched control subjects for personal and family history of skin cancer, phenotypic markers, sunburn history, and training habits. All subjects underwent a total body skin examination.

Most runners reported that they trained and competed wearing shorts that left the legs uncovered and shirts that left the arms and upper back uncovered or only partially covered. Only about half said they regularly used sunscreen.

Control subjects showed higher sun sensitivity than did runners, with more cases of light eye color and of Fitzpatrick skin types I or II. Control subjects also had more melanocytic nevi. The runners, however, were found to have significantly more atypical nevi and solar lentigines, Dr. Ambros-Rudolph and her associates said.

Runners also were significantly more likely to be referred for surgical removal of suspicious lesions, including basal cell carcinomas, squamous cell carcinomas, and actinic keratoses.

The number of atypical nevi, solar lentigines, and suspicious lesions was highest in the runners who spent the most time training outdoors, they reported.

Exercise-induced immunosuppression commonly seen in endurance athletes may contribute to the higher risk of malignant melanoma in marathon runners, the researchers said.

In addition, professional athletes in other outdoor sports have been shown to receive over 30 times the daily limit of UV exposure recommended by the International Commission on Non-Ionizing Radiation Protection and the American Conference of Governmental Industrial Hygienists. Moreover, sweating during exercise has been shown to increase the photosensitivity of the skin, presumably via hydration of the horny layer and shifting in the stratum corneum UV absorption spectrum, Dr. Ambros-Rudolph and her associates noted.

White marathon runners are at significantly higher risk of developing malignant melanoma than are white people of the same age who don't spend 40 or more hours per week training or competing outdoors, reported Dr. Christina M. Ambros-Rudolph and her associates at the Medical University of Graz (Austria).

Compared with an age-, sex-, and race-matched control population, marathon runners were found to have significantly more atypical melanocytic nevi and solar lentigines. Their referral rate for removal of lesions suggestive of nonmelanoma skin cancer also was significantly higher than that of control subjects.

Both the number of lesions and the rate of referral for surgical excision increased as the number of hours spent training outdoors increased, the researchers said (Arch. Dermatol. 2006;142:1471–4).

Physicians should alert patients who are runners to “the crucial role of UV radiation in the development of malignant melanoma and nonmalignant skin cancers. In particular, they should be advised to reduce UV exposure during exercising by choosing training and competition schedules with low sun exposure, wearing adequate clothing, and regularly using water-resistant sunscreens,” Dr. Ambros-Rudolph and her associates said.

They became concerned about malignant melanoma incidence among runners when they observed eight cases of the disease in marathoners treated in their dermatology department over the past decade. The researchers are themselves “enthusiastic runners,” and two are regular marathoners, they noted.

In all eight cases, melanomas developed in areas that were uncovered or only partially covered by clothing—the upper back, lower thigh, and calf—and all but one were associated with an atypical or congenital melanocytic nevus.

To study the issue, the investigators assessed 210 white marathon runners (166 men and 44 women) aged 19–71 years and 210 white age- and sex-matched control subjects for personal and family history of skin cancer, phenotypic markers, sunburn history, and training habits. All subjects underwent a total body skin examination.

Most runners reported that they trained and competed wearing shorts that left the legs uncovered and shirts that left the arms and upper back uncovered or only partially covered. Only about half said they regularly used sunscreen.

Control subjects showed higher sun sensitivity than did runners, with more cases of light eye color and of Fitzpatrick skin types I or II. Control subjects also had more melanocytic nevi. The runners, however, were found to have significantly more atypical nevi and solar lentigines, Dr. Ambros-Rudolph and her associates said.

Runners also were significantly more likely to be referred for surgical removal of suspicious lesions, including basal cell carcinomas, squamous cell carcinomas, and actinic keratoses.

The number of atypical nevi, solar lentigines, and suspicious lesions was highest in the runners who spent the most time training outdoors, they reported.

Exercise-induced immunosuppression commonly seen in endurance athletes may contribute to the higher risk of malignant melanoma in marathon runners, the researchers said.

In addition, professional athletes in other outdoor sports have been shown to receive over 30 times the daily limit of UV exposure recommended by the International Commission on Non-Ionizing Radiation Protection and the American Conference of Governmental Industrial Hygienists. Moreover, sweating during exercise has been shown to increase the photosensitivity of the skin, presumably via hydration of the horny layer and shifting in the stratum corneum UV absorption spectrum, Dr. Ambros-Rudolph and her associates noted.

White marathon runners are at significantly higher risk of developing malignant melanoma than are white people of the same age who don't spend 40 or more hours per week training or competing outdoors, reported Dr. Christina M. Ambros-Rudolph and her associates at the Medical University of Graz (Austria).

Compared with an age-, sex-, and race-matched control population, marathon runners were found to have significantly more atypical melanocytic nevi and solar lentigines. Their referral rate for removal of lesions suggestive of nonmelanoma skin cancer also was significantly higher than that of control subjects.

Both the number of lesions and the rate of referral for surgical excision increased as the number of hours spent training outdoors increased, the researchers said (Arch. Dermatol. 2006;142:1471–4).

Physicians should alert patients who are runners to “the crucial role of UV radiation in the development of malignant melanoma and nonmalignant skin cancers. In particular, they should be advised to reduce UV exposure during exercising by choosing training and competition schedules with low sun exposure, wearing adequate clothing, and regularly using water-resistant sunscreens,” Dr. Ambros-Rudolph and her associates said.

They became concerned about malignant melanoma incidence among runners when they observed eight cases of the disease in marathoners treated in their dermatology department over the past decade. The researchers are themselves “enthusiastic runners,” and two are regular marathoners, they noted.

In all eight cases, melanomas developed in areas that were uncovered or only partially covered by clothing—the upper back, lower thigh, and calf—and all but one were associated with an atypical or congenital melanocytic nevus.

To study the issue, the investigators assessed 210 white marathon runners (166 men and 44 women) aged 19–71 years and 210 white age- and sex-matched control subjects for personal and family history of skin cancer, phenotypic markers, sunburn history, and training habits. All subjects underwent a total body skin examination.

Most runners reported that they trained and competed wearing shorts that left the legs uncovered and shirts that left the arms and upper back uncovered or only partially covered. Only about half said they regularly used sunscreen.

Control subjects showed higher sun sensitivity than did runners, with more cases of light eye color and of Fitzpatrick skin types I or II. Control subjects also had more melanocytic nevi. The runners, however, were found to have significantly more atypical nevi and solar lentigines, Dr. Ambros-Rudolph and her associates said.

Runners also were significantly more likely to be referred for surgical removal of suspicious lesions, including basal cell carcinomas, squamous cell carcinomas, and actinic keratoses.

The number of atypical nevi, solar lentigines, and suspicious lesions was highest in the runners who spent the most time training outdoors, they reported.

Exercise-induced immunosuppression commonly seen in endurance athletes may contribute to the higher risk of malignant melanoma in marathon runners, the researchers said.

In addition, professional athletes in other outdoor sports have been shown to receive over 30 times the daily limit of UV exposure recommended by the International Commission on Non-Ionizing Radiation Protection and the American Conference of Governmental Industrial Hygienists. Moreover, sweating during exercise has been shown to increase the photosensitivity of the skin, presumably via hydration of the horny layer and shifting in the stratum corneum UV absorption spectrum, Dr. Ambros-Rudolph and her associates noted.

Air travel has finally been shown to influence the spread of influenza, said Dr. John S. Brownstein of the Children's Hospital Informatics Program at the Harvard-MIT division of health sciences and technology, Boston, and his associates.

They analyzed interregional influenza spread across the United States, then correlated the pattern with data on airline travel. Previous studies that used computer simulations have suggested that air travel may play a role in the spread of annual influenza, but “we provide what is to our knowledge the first empirical evidence to confirm the effect airline volume [has] on long-range spread,” they said.

The investigators analyzed weekly influenza mortality data from the Centers for Disease Control and Prevention for nine influenza seasons between 1996–1997 and 2004–2005. They found strong correlations between monthly fluctuations in airline volume and two other measures: the rate of disease spread and the timing of seasonal influenza mortality.

The number of domestic passengers from November to January of a given season showed a strong inverse correlation with the time to the spread of influenza across the United States. “Although influenza activity is highest between January and March, initial regional seeding of infection may occur earlier,” Dr. Brownstein and his associates said (PLoS Med. 2006 October [Epubdoi:10.1371/journal.pmed.0030401]).

“Our results suggest that for a nonpandemic year, travel during the Thanksgiving holiday may be central to the yearly national spread of influenza in the [United States],” they noted. The volume of international travel in all three months, but particularly in September, predicted the national seasonal peak in influenza mortality.

These findings suggest that airline passenger volume accounts for about 60% of the between-season variation in influenza spread and peak.

“Our results suggest that limiting domestic airline volume would have a measurable impact on the rate of spread of an influenza pandemic.” Restricting international flights into the United States also would reduce the probability of a pandemic strain reaching the country.

Air travel has finally been shown to influence the spread of influenza, said Dr. John S. Brownstein of the Children's Hospital Informatics Program at the Harvard-MIT division of health sciences and technology, Boston, and his associates.

They analyzed interregional influenza spread across the United States, then correlated the pattern with data on airline travel. Previous studies that used computer simulations have suggested that air travel may play a role in the spread of annual influenza, but “we provide what is to our knowledge the first empirical evidence to confirm the effect airline volume [has] on long-range spread,” they said.

The investigators analyzed weekly influenza mortality data from the Centers for Disease Control and Prevention for nine influenza seasons between 1996–1997 and 2004–2005. They found strong correlations between monthly fluctuations in airline volume and two other measures: the rate of disease spread and the timing of seasonal influenza mortality.

The number of domestic passengers from November to January of a given season showed a strong inverse correlation with the time to the spread of influenza across the United States. “Although influenza activity is highest between January and March, initial regional seeding of infection may occur earlier,” Dr. Brownstein and his associates said (PLoS Med. 2006 October [Epubdoi:10.1371/journal.pmed.0030401]).

“Our results suggest that for a nonpandemic year, travel during the Thanksgiving holiday may be central to the yearly national spread of influenza in the [United States],” they noted. The volume of international travel in all three months, but particularly in September, predicted the national seasonal peak in influenza mortality.

These findings suggest that airline passenger volume accounts for about 60% of the between-season variation in influenza spread and peak.

“Our results suggest that limiting domestic airline volume would have a measurable impact on the rate of spread of an influenza pandemic.” Restricting international flights into the United States also would reduce the probability of a pandemic strain reaching the country.

Air travel has finally been shown to influence the spread of influenza, said Dr. John S. Brownstein of the Children's Hospital Informatics Program at the Harvard-MIT division of health sciences and technology, Boston, and his associates.

They analyzed interregional influenza spread across the United States, then correlated the pattern with data on airline travel. Previous studies that used computer simulations have suggested that air travel may play a role in the spread of annual influenza, but “we provide what is to our knowledge the first empirical evidence to confirm the effect airline volume [has] on long-range spread,” they said.

The investigators analyzed weekly influenza mortality data from the Centers for Disease Control and Prevention for nine influenza seasons between 1996–1997 and 2004–2005. They found strong correlations between monthly fluctuations in airline volume and two other measures: the rate of disease spread and the timing of seasonal influenza mortality.

The number of domestic passengers from November to January of a given season showed a strong inverse correlation with the time to the spread of influenza across the United States. “Although influenza activity is highest between January and March, initial regional seeding of infection may occur earlier,” Dr. Brownstein and his associates said (PLoS Med. 2006 October [Epubdoi:10.1371/journal.pmed.0030401]).

“Our results suggest that for a nonpandemic year, travel during the Thanksgiving holiday may be central to the yearly national spread of influenza in the [United States],” they noted. The volume of international travel in all three months, but particularly in September, predicted the national seasonal peak in influenza mortality.

These findings suggest that airline passenger volume accounts for about 60% of the between-season variation in influenza spread and peak.

“Our results suggest that limiting domestic airline volume would have a measurable impact on the rate of spread of an influenza pandemic.” Restricting international flights into the United States also would reduce the probability of a pandemic strain reaching the country.

Older men who have low testosterone levels are at substantially higher risk of falling than are their peers who have normal or high levels, reported Dr. Eric Orwoll and his associates in the Osteoporotic Fractures in Men study, which is known as MrOS.

Several of the factors associated with increased risk of falling—including reduced muscle mass, decreased muscle strength, and decreased physical performance—are thought to be linked to age-related declines in androgen levels, but “no prospective data document this association,” Dr. Orwoll, of Oregon Health and Science University, Portland, and his associates said in the Oct. 23 issue of the Archives of Internal Medicine.

They examined the issue using data from the MrOS study, a multicenter community-based cohort study of approximately 6,000 men aged 65 and older that was designed to identify risk factors for falls and fractures.

A subgroup of 2,623 subjects who were followed at 4-month intervals for a mean of 4 years formed the basis of the study. The mean age was 73 years, and most of the participants rated their general health as good to excellent.

Falls were very common, with 56% of the men reporting at least one fall over the course of follow-up. Falls were more common at older ages, with more than 20% of the men over age 80 reporting that they had fallen five times or more, compared with only 10% of men aged 65–69 years.

The risk of falling increased in men with declining levels of bioavailable testosterone.

“Fall risk in men in the lowest quartile of baseline bioavailable testosterone concentration was more than 40% greater than that in men in the highest quartile, [both] before and after adjustment for physical performance,” Dr. Orwoll and his associates noted (Arch. Intern. Med. 2006;166: 2124–31).

When they repeated their analysis using data on only the healthiest subjects, this association did not change.

Men with lower testosterone levels also were at higher risk for multiple falls (more than 2 per year).

The risk of falls was also greater in men who had reduced levels of muscle strength or physical function.

However, when these factors were statistically controlled for, the effect of testosterone level on fall risk was unchanged. This demonstrates that the association between testosterone level and fall risk is strong regardless of the subject's physical performance and muscle strength.

“There may be other androgen-dependent mechanisms that contribute to the causation of falling,” such as testosterone's effects on visual performance, cognition, or neuromuscular coordination, the investigators noted.

Given that their large study population was geographically and racially diverse, the study findings “are likely to be broadly applicable to similarly aged, generally healthy U.S. men,” the researchers pointed out.

“These results provide additional justification for trials of testosterone supplementation in older men,” Dr. Orwoll and his associates said.

Older men who have low testosterone levels are at substantially higher risk of falling than are their peers who have normal or high levels, reported Dr. Eric Orwoll and his associates in the Osteoporotic Fractures in Men study, which is known as MrOS.

Several of the factors associated with increased risk of falling—including reduced muscle mass, decreased muscle strength, and decreased physical performance—are thought to be linked to age-related declines in androgen levels, but “no prospective data document this association,” Dr. Orwoll, of Oregon Health and Science University, Portland, and his associates said in the Oct. 23 issue of the Archives of Internal Medicine.

They examined the issue using data from the MrOS study, a multicenter community-based cohort study of approximately 6,000 men aged 65 and older that was designed to identify risk factors for falls and fractures.

A subgroup of 2,623 subjects who were followed at 4-month intervals for a mean of 4 years formed the basis of the study. The mean age was 73 years, and most of the participants rated their general health as good to excellent.

Falls were very common, with 56% of the men reporting at least one fall over the course of follow-up. Falls were more common at older ages, with more than 20% of the men over age 80 reporting that they had fallen five times or more, compared with only 10% of men aged 65–69 years.

The risk of falling increased in men with declining levels of bioavailable testosterone.

“Fall risk in men in the lowest quartile of baseline bioavailable testosterone concentration was more than 40% greater than that in men in the highest quartile, [both] before and after adjustment for physical performance,” Dr. Orwoll and his associates noted (Arch. Intern. Med. 2006;166: 2124–31).

When they repeated their analysis using data on only the healthiest subjects, this association did not change.

Men with lower testosterone levels also were at higher risk for multiple falls (more than 2 per year).

The risk of falls was also greater in men who had reduced levels of muscle strength or physical function.

However, when these factors were statistically controlled for, the effect of testosterone level on fall risk was unchanged. This demonstrates that the association between testosterone level and fall risk is strong regardless of the subject's physical performance and muscle strength.

“There may be other androgen-dependent mechanisms that contribute to the causation of falling,” such as testosterone's effects on visual performance, cognition, or neuromuscular coordination, the investigators noted.

Given that their large study population was geographically and racially diverse, the study findings “are likely to be broadly applicable to similarly aged, generally healthy U.S. men,” the researchers pointed out.

“These results provide additional justification for trials of testosterone supplementation in older men,” Dr. Orwoll and his associates said.

Older men who have low testosterone levels are at substantially higher risk of falling than are their peers who have normal or high levels, reported Dr. Eric Orwoll and his associates in the Osteoporotic Fractures in Men study, which is known as MrOS.

Several of the factors associated with increased risk of falling—including reduced muscle mass, decreased muscle strength, and decreased physical performance—are thought to be linked to age-related declines in androgen levels, but “no prospective data document this association,” Dr. Orwoll, of Oregon Health and Science University, Portland, and his associates said in the Oct. 23 issue of the Archives of Internal Medicine.

They examined the issue using data from the MrOS study, a multicenter community-based cohort study of approximately 6,000 men aged 65 and older that was designed to identify risk factors for falls and fractures.

A subgroup of 2,623 subjects who were followed at 4-month intervals for a mean of 4 years formed the basis of the study. The mean age was 73 years, and most of the participants rated their general health as good to excellent.

Falls were very common, with 56% of the men reporting at least one fall over the course of follow-up. Falls were more common at older ages, with more than 20% of the men over age 80 reporting that they had fallen five times or more, compared with only 10% of men aged 65–69 years.

The risk of falling increased in men with declining levels of bioavailable testosterone.

“Fall risk in men in the lowest quartile of baseline bioavailable testosterone concentration was more than 40% greater than that in men in the highest quartile, [both] before and after adjustment for physical performance,” Dr. Orwoll and his associates noted (Arch. Intern. Med. 2006;166: 2124–31).

When they repeated their analysis using data on only the healthiest subjects, this association did not change.

Men with lower testosterone levels also were at higher risk for multiple falls (more than 2 per year).

The risk of falls was also greater in men who had reduced levels of muscle strength or physical function.

However, when these factors were statistically controlled for, the effect of testosterone level on fall risk was unchanged. This demonstrates that the association between testosterone level and fall risk is strong regardless of the subject's physical performance and muscle strength.

“There may be other androgen-dependent mechanisms that contribute to the causation of falling,” such as testosterone's effects on visual performance, cognition, or neuromuscular coordination, the investigators noted.

Given that their large study population was geographically and racially diverse, the study findings “are likely to be broadly applicable to similarly aged, generally healthy U.S. men,” the researchers pointed out.

“These results provide additional justification for trials of testosterone supplementation in older men,” Dr. Orwoll and his associates said.

Survivors of childhood cancer—particularly those who have undergone total body irradiation in preparation for bone marrow transplant—have increased rates of hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in adolescence and young adulthood, reported Dr. Kristen Neville of the University of New South Wales, Sydney, and her associates.

The researchers assessed 248 survivors of childhood cancer who had been treated initially at Sydney Children's Hospital during 1971–2000 and had regularly attended follow-up clinics.

Overall, 18% of the survivors had developed hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus by the time they reached puberty or young adulthood. Many were asymptomatic and were diagnosed only because they were screened for this study, Dr. Neville and her associates said.

The findings suggest that a metabolic abnormality becomes established early in these individuals, and that a simple measurement of the waist-to-height ratio can be used to screen for that abnormality well before it emerges clinically years later. Early dietary and lifestyle interventions might then prevent or delay the onset of hyperinsulinemia, impaired glucose tolerance, and frank diabetes, the investigators said (J. Clin. Endocrinol. Metab. 2006;91:4401–7). The results also indicated that some survivors of childhood cancer begin showing increased abdominal adiposity and adverse lipid changes before or during puberty, even though their rates of overweight and obesity are the same as those of control subjects at that age.

At the time when the cancer survivors were evaluated for this study, in 2002–2004, their median age was 18 years, and the median interval since cancer diagnosis was 13 years; 36 subjects were prepubertal, 88 were pubertal, and 124 were young adults. The subjects were at least 2 years past their cancer diagnoses and had been disease free for a minimum of 1 year.

Patients who had undergone bone marrow transplantation accounted for more than half of those who had developed diabetes, hyperinsulinemia, or impaired glucose tolerance. This suggests that total body irradiation conditioning should be reconsidered. “If alternative conditioning therapies for bone marrow transplant can be considered without compromising survival, the risk of metabolic abnormality may be decreased,” the investigators said.

The median fasting insulin levels in the prepubertal and pubertal subjects were approximately twice those of controls. In addition, 23% of the pubertal subjects had hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus, compared with none of the controls in that age group.

The prevalence of abdominal adiposity among the prepubertal and pubertal cancer survivors was double that of matched control subjects. The cancer survivors had similar body mass index values, but higher waist:height ratios. Accumulation of abdominal fat was also seen in the adult cancer survivors.

This suggests that rather than a high BMI, a waist:height ratio of 0.5 or greater “may be an early and simple clinical marker for the later development of the metabolic disturbance,” the researchers noted.

Survivors of childhood cancer—particularly those who have undergone total body irradiation in preparation for bone marrow transplant—have increased rates of hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in adolescence and young adulthood, reported Dr. Kristen Neville of the University of New South Wales, Sydney, and her associates.

The researchers assessed 248 survivors of childhood cancer who had been treated initially at Sydney Children's Hospital during 1971–2000 and had regularly attended follow-up clinics.

Overall, 18% of the survivors had developed hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus by the time they reached puberty or young adulthood. Many were asymptomatic and were diagnosed only because they were screened for this study, Dr. Neville and her associates said.

The findings suggest that a metabolic abnormality becomes established early in these individuals, and that a simple measurement of the waist-to-height ratio can be used to screen for that abnormality well before it emerges clinically years later. Early dietary and lifestyle interventions might then prevent or delay the onset of hyperinsulinemia, impaired glucose tolerance, and frank diabetes, the investigators said (J. Clin. Endocrinol. Metab. 2006;91:4401–7). The results also indicated that some survivors of childhood cancer begin showing increased abdominal adiposity and adverse lipid changes before or during puberty, even though their rates of overweight and obesity are the same as those of control subjects at that age.

At the time when the cancer survivors were evaluated for this study, in 2002–2004, their median age was 18 years, and the median interval since cancer diagnosis was 13 years; 36 subjects were prepubertal, 88 were pubertal, and 124 were young adults. The subjects were at least 2 years past their cancer diagnoses and had been disease free for a minimum of 1 year.

Patients who had undergone bone marrow transplantation accounted for more than half of those who had developed diabetes, hyperinsulinemia, or impaired glucose tolerance. This suggests that total body irradiation conditioning should be reconsidered. “If alternative conditioning therapies for bone marrow transplant can be considered without compromising survival, the risk of metabolic abnormality may be decreased,” the investigators said.

The median fasting insulin levels in the prepubertal and pubertal subjects were approximately twice those of controls. In addition, 23% of the pubertal subjects had hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus, compared with none of the controls in that age group.

The prevalence of abdominal adiposity among the prepubertal and pubertal cancer survivors was double that of matched control subjects. The cancer survivors had similar body mass index values, but higher waist:height ratios. Accumulation of abdominal fat was also seen in the adult cancer survivors.

This suggests that rather than a high BMI, a waist:height ratio of 0.5 or greater “may be an early and simple clinical marker for the later development of the metabolic disturbance,” the researchers noted.

Survivors of childhood cancer—particularly those who have undergone total body irradiation in preparation for bone marrow transplant—have increased rates of hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in adolescence and young adulthood, reported Dr. Kristen Neville of the University of New South Wales, Sydney, and her associates.

The researchers assessed 248 survivors of childhood cancer who had been treated initially at Sydney Children's Hospital during 1971–2000 and had regularly attended follow-up clinics.

Overall, 18% of the survivors had developed hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus by the time they reached puberty or young adulthood. Many were asymptomatic and were diagnosed only because they were screened for this study, Dr. Neville and her associates said.

The findings suggest that a metabolic abnormality becomes established early in these individuals, and that a simple measurement of the waist-to-height ratio can be used to screen for that abnormality well before it emerges clinically years later. Early dietary and lifestyle interventions might then prevent or delay the onset of hyperinsulinemia, impaired glucose tolerance, and frank diabetes, the investigators said (J. Clin. Endocrinol. Metab. 2006;91:4401–7). The results also indicated that some survivors of childhood cancer begin showing increased abdominal adiposity and adverse lipid changes before or during puberty, even though their rates of overweight and obesity are the same as those of control subjects at that age.

At the time when the cancer survivors were evaluated for this study, in 2002–2004, their median age was 18 years, and the median interval since cancer diagnosis was 13 years; 36 subjects were prepubertal, 88 were pubertal, and 124 were young adults. The subjects were at least 2 years past their cancer diagnoses and had been disease free for a minimum of 1 year.

Patients who had undergone bone marrow transplantation accounted for more than half of those who had developed diabetes, hyperinsulinemia, or impaired glucose tolerance. This suggests that total body irradiation conditioning should be reconsidered. “If alternative conditioning therapies for bone marrow transplant can be considered without compromising survival, the risk of metabolic abnormality may be decreased,” the investigators said.

The median fasting insulin levels in the prepubertal and pubertal subjects were approximately twice those of controls. In addition, 23% of the pubertal subjects had hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus, compared with none of the controls in that age group.

The prevalence of abdominal adiposity among the prepubertal and pubertal cancer survivors was double that of matched control subjects. The cancer survivors had similar body mass index values, but higher waist:height ratios. Accumulation of abdominal fat was also seen in the adult cancer survivors.

This suggests that rather than a high BMI, a waist:height ratio of 0.5 or greater “may be an early and simple clinical marker for the later development of the metabolic disturbance,” the researchers noted.

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

Anxiety disorders are associated with a broad range of physical conditions, including respiratory diseases, gastrointestinal diseases, arthritic conditions, allergic conditions, thyroid diseases, and migraines, reported Dr. Jitender Sareen of the University of Manitoba, Winnipeg, and his associates.

The researchers conducted what they described as the first study aimed at systematically evaluating the association between anxiety disorders and physical conditions in a large epidemiologic sample that included standardized physician-based diagnoses. They used data from the German Health Survey, a nationally representative sample of more than 4,000 members of the German population aged 18–79 years in 1997–1999.

Subjects were assessed for 44 physical conditions and for panic disorder, agoraphobia, social phobia, simple phobia, generalized anxiety disorder, and obsessive-compulsive disorder, Dr. Sareen and his associates reported.

The presence of an anxiety disorder was associated with respiratory diseases such as asthma and chronic bronchitis; gastrointestinal diseases such as gastritis and ulcer; arthritic conditions such as inflammatory joint disease; allergic conditions such as hay fever, eczema, hives, food allergy, and conjunctivitis; thyroid diseases; and migraine headaches.

Anxiety disorders were not found to be associated with cardiac disease, hypertension, or diabetes in this study.

In most cases of comorbidity, onset of the anxiety disorder preceded onset of the physical conditions, the investigators said (Arch. Intern. Med. 2006;166:2109–16).

Compared with subjects who had these physical conditions alone, those who had comorbid anxiety disorders were more likely to report a poor quality of life and significant disability because of the physical illness.

“These findings underscore the importance of recognition of comorbidity of anxiety disorders among people who present with these physical health problems,” Dr. Sareen and his associates said.

The nature of this link between anxiety disorders and physical illnesses remains unclear. There may be a direct causal relationship mediated by biological mechanisms. Or there may be common genetic, environmental, or personality factors that underlie both types of disorders, the investigators noted.

Anxiety disorders are associated with a broad range of physical conditions, including respiratory diseases, gastrointestinal diseases, arthritic conditions, allergic conditions, thyroid diseases, and migraines, reported Dr. Jitender Sareen of the University of Manitoba, Winnipeg, and his associates.

The researchers conducted what they described as the first study aimed at systematically evaluating the association between anxiety disorders and physical conditions in a large epidemiologic sample that included standardized physician-based diagnoses. They used data from the German Health Survey, a nationally representative sample of more than 4,000 members of the German population aged 18–79 years in 1997–1999.

Subjects were assessed for 44 physical conditions and for panic disorder, agoraphobia, social phobia, simple phobia, generalized anxiety disorder, and obsessive-compulsive disorder, Dr. Sareen and his associates reported.

The presence of an anxiety disorder was associated with respiratory diseases such as asthma and chronic bronchitis; gastrointestinal diseases such as gastritis and ulcer; arthritic conditions such as inflammatory joint disease; allergic conditions such as hay fever, eczema, hives, food allergy, and conjunctivitis; thyroid diseases; and migraine headaches.

Anxiety disorders were not found to be associated with cardiac disease, hypertension, or diabetes in this study.

In most cases of comorbidity, onset of the anxiety disorder preceded onset of the physical conditions, the investigators said (Arch. Intern. Med. 2006;166:2109–16).

Compared with subjects who had these physical conditions alone, those who had comorbid anxiety disorders were more likely to report a poor quality of life and significant disability because of the physical illness.

“These findings underscore the importance of recognition of comorbidity of anxiety disorders among people who present with these physical health problems,” Dr. Sareen and his associates said.

The nature of this link between anxiety disorders and physical illnesses remains unclear. There may be a direct causal relationship mediated by biological mechanisms. Or there may be common genetic, environmental, or personality factors that underlie both types of disorders, the investigators noted.

Anxiety disorders are associated with a broad range of physical conditions, including respiratory diseases, gastrointestinal diseases, arthritic conditions, allergic conditions, thyroid diseases, and migraines, reported Dr. Jitender Sareen of the University of Manitoba, Winnipeg, and his associates.

The researchers conducted what they described as the first study aimed at systematically evaluating the association between anxiety disorders and physical conditions in a large epidemiologic sample that included standardized physician-based diagnoses. They used data from the German Health Survey, a nationally representative sample of more than 4,000 members of the German population aged 18–79 years in 1997–1999.

Subjects were assessed for 44 physical conditions and for panic disorder, agoraphobia, social phobia, simple phobia, generalized anxiety disorder, and obsessive-compulsive disorder, Dr. Sareen and his associates reported.

The presence of an anxiety disorder was associated with respiratory diseases such as asthma and chronic bronchitis; gastrointestinal diseases such as gastritis and ulcer; arthritic conditions such as inflammatory joint disease; allergic conditions such as hay fever, eczema, hives, food allergy, and conjunctivitis; thyroid diseases; and migraine headaches.

Anxiety disorders were not found to be associated with cardiac disease, hypertension, or diabetes in this study.

In most cases of comorbidity, onset of the anxiety disorder preceded onset of the physical conditions, the investigators said (Arch. Intern. Med. 2006;166:2109–16).

Compared with subjects who had these physical conditions alone, those who had comorbid anxiety disorders were more likely to report a poor quality of life and significant disability because of the physical illness.

“These findings underscore the importance of recognition of comorbidity of anxiety disorders among people who present with these physical health problems,” Dr. Sareen and his associates said.

The nature of this link between anxiety disorders and physical illnesses remains unclear. There may be a direct causal relationship mediated by biological mechanisms. Or there may be common genetic, environmental, or personality factors that underlie both types of disorders, the investigators noted.

Psoriasis appears to be an independent risk factor for myocardial infarction, conferring the same magnitude of risk as other major cardiac risk factors, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, and his associates.

Noting that the immunologic abnormalities that give rise to psoriasis may also put patients at risk for other diseases associated with systemic inflammation, including heart disease, Dr. Gelfand and his associates assessed the risk of MI in a population-based cohort study. They used data on nearly 131,000 psoriasis patients treated in the United Kingdom between 1987 and 2002, who were matched with 557,000 control subjects.

After a mean of 5 years, patients with psoriasis had a significantly higher incidence of MI than controls. In those younger than 50 years, psoriasis conferred a similar degree of risk as standard cardiac risk factors. Patients with the most severe psoriasis had the highest MI rate. These findings are consistent with the hypothesis that greater immune activity in psoriasis is related to a higher risk of MI (JAMA 2006;296:1735–41).

The link between psoriasis and MI persisted after the data were adjusted for smoking, diabetes, hyperlipidemia, hypertension, and body mass index, and also appeared to be independent of psoriasis treatments, such as oral retinoids, cyclosporine, and methotrexate. The researchers were not able to examine the role of NSAIDs.

“The link between psoriasis and MI may be mediated by other factors beyond inflammation, such as psychological stress, sedentary lifestyle, or possibly poor compliance with management of CV risk factors,” Dr. Gelfand and his associates noted.

Psoriasis appears to be an independent risk factor for myocardial infarction, conferring the same magnitude of risk as other major cardiac risk factors, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, and his associates.

Noting that the immunologic abnormalities that give rise to psoriasis may also put patients at risk for other diseases associated with systemic inflammation, including heart disease, Dr. Gelfand and his associates assessed the risk of MI in a population-based cohort study. They used data on nearly 131,000 psoriasis patients treated in the United Kingdom between 1987 and 2002, who were matched with 557,000 control subjects.

After a mean of 5 years, patients with psoriasis had a significantly higher incidence of MI than controls. In those younger than 50 years, psoriasis conferred a similar degree of risk as standard cardiac risk factors. Patients with the most severe psoriasis had the highest MI rate. These findings are consistent with the hypothesis that greater immune activity in psoriasis is related to a higher risk of MI (JAMA 2006;296:1735–41).

The link between psoriasis and MI persisted after the data were adjusted for smoking, diabetes, hyperlipidemia, hypertension, and body mass index, and also appeared to be independent of psoriasis treatments, such as oral retinoids, cyclosporine, and methotrexate. The researchers were not able to examine the role of NSAIDs.

“The link between psoriasis and MI may be mediated by other factors beyond inflammation, such as psychological stress, sedentary lifestyle, or possibly poor compliance with management of CV risk factors,” Dr. Gelfand and his associates noted.

Psoriasis appears to be an independent risk factor for myocardial infarction, conferring the same magnitude of risk as other major cardiac risk factors, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, and his associates.

Noting that the immunologic abnormalities that give rise to psoriasis may also put patients at risk for other diseases associated with systemic inflammation, including heart disease, Dr. Gelfand and his associates assessed the risk of MI in a population-based cohort study. They used data on nearly 131,000 psoriasis patients treated in the United Kingdom between 1987 and 2002, who were matched with 557,000 control subjects.

After a mean of 5 years, patients with psoriasis had a significantly higher incidence of MI than controls. In those younger than 50 years, psoriasis conferred a similar degree of risk as standard cardiac risk factors. Patients with the most severe psoriasis had the highest MI rate. These findings are consistent with the hypothesis that greater immune activity in psoriasis is related to a higher risk of MI (JAMA 2006;296:1735–41).

The link between psoriasis and MI persisted after the data were adjusted for smoking, diabetes, hyperlipidemia, hypertension, and body mass index, and also appeared to be independent of psoriasis treatments, such as oral retinoids, cyclosporine, and methotrexate. The researchers were not able to examine the role of NSAIDs.

“The link between psoriasis and MI may be mediated by other factors beyond inflammation, such as psychological stress, sedentary lifestyle, or possibly poor compliance with management of CV risk factors,” Dr. Gelfand and his associates noted.

Medical induction of labor appears to double the risk of amniotic fluid embolism, reported Dr. Michael S. Kramer of Montreal Children's Hospital and his associates.

Findings from their retrospective cohort study of approximately 3 million hospital births throughout Canada between 1991 and 2002 “support the long-standing, but heretofore unsubstantiated, suspicion that labour induction increases the risk of this rare but serious maternal complication.

“Although the small absolute risk of amniotic fluid embolism is unlikely to affect the decision to induce labour in the presence of compelling clinical indications, women and physicians should be aware of this risk if the decision is elective,” the researchers said in the Oct. 21 issue of the Lancet.

“We should emphasise that the absolute risk increase of amniotic fluid embolism for women undergoing medical induction of labour is very small: 4 or 5 total cases and 1 or 2 fatal cases per 100,000 women induced.

“However, with 4 million births per year and induction rates approaching 20% in the [United States], this practice could be causing amniotic fluid embolism in 30–40 women per year in the [United States] alone (including 10–15 deaths),” Dr. Kramer and his associates added (Lancet 2006;368:1444–8).

Despite being rare, amniotic fluid embolism is one of the leading causes of maternal mortality in developed countries, ahead of postpartum hemorrhage and other pulmonary embolisms. The cause of this catastrophic complication is not well understood. “It is thought to arise from a simultaneous tear in the fetal membranes and uterine vessels, through which amniotic fluid can pass into the uterine venous circulation and hence to the maternal pulmonary arterial circulation,” the researchers said.

Strong uterine contractions are believed to raise the risk of amniotic fluid embolism, and induction and augmentation of labor have been proposed as possible contributing factors.

In their epidemiologic study of the association between drug-induced labor and amniotic fluid embolism, there were 180 cases of this condition, including 24 fatal cases, yielding a total rate of 6/100,000 singleton deliveries and a fatal rate of 0.8/100,000 singleton deliveries.

The rate was almost twice as high in women who had undergone medical induction of labor as in those who had not. This association remained robust after the data were adjusted to account for many other potential risk factors, such as maternal age, presentation, delivery method, previous cesarean delivery, pregnancy complications, and labor complications.

This finding “should be a cause for concern in view of the increasing tendency for clinicians to induce labour, and especially for routine induction at term or after term,” the investigators said.

They also found that multiple pregnancy, older maternal age, cesarean delivery, forceps- or vacuum-assisted delivery, eclampsia, polyhydramnios, placenta previa, placental abruption, cervical laceration, uterine rupture, and fetal distress all raised the risk of amniotic fluid embolism, though not to the degree that drug-induced labor did. Many of these risk factors could be directly related to “the presumed causal roles of strong uterine contractions, excess amniotic fluid, and disruption of the uterine vasculature,” the researchers noted.

Moreover, the link between amniotic embolism on the one hand and cesarean or instrumental vaginal delivery on the other “might simply reflect the difficult labours that led to these procedures, rather than true effects of the procedures themselves.”

In particular, “the very strong association with caesarean delivery could also indicate reverse causality (i.e., the caesarean could have been a consequence of the signs and symptoms of amniotic fluid embolism,” Dr. Kramer and his associates pointed out.

The rates of total and fatal amniotic fluid embolism did not increase over time in this study, even though the rate of medically induced labor did increase. This probably reflects the rarity of the disorder, or it could be because of the concomitant decrease in other risk factors, such as forceps delivery, they added.

Medical induction of labor appears to double the risk of amniotic fluid embolism, reported Dr. Michael S. Kramer of Montreal Children's Hospital and his associates.

Findings from their retrospective cohort study of approximately 3 million hospital births throughout Canada between 1991 and 2002 “support the long-standing, but heretofore unsubstantiated, suspicion that labour induction increases the risk of this rare but serious maternal complication.

“Although the small absolute risk of amniotic fluid embolism is unlikely to affect the decision to induce labour in the presence of compelling clinical indications, women and physicians should be aware of this risk if the decision is elective,” the researchers said in the Oct. 21 issue of the Lancet.

“We should emphasise that the absolute risk increase of amniotic fluid embolism for women undergoing medical induction of labour is very small: 4 or 5 total cases and 1 or 2 fatal cases per 100,000 women induced.

“However, with 4 million births per year and induction rates approaching 20% in the [United States], this practice could be causing amniotic fluid embolism in 30–40 women per year in the [United States] alone (including 10–15 deaths),” Dr. Kramer and his associates added (Lancet 2006;368:1444–8).

Despite being rare, amniotic fluid embolism is one of the leading causes of maternal mortality in developed countries, ahead of postpartum hemorrhage and other pulmonary embolisms. The cause of this catastrophic complication is not well understood. “It is thought to arise from a simultaneous tear in the fetal membranes and uterine vessels, through which amniotic fluid can pass into the uterine venous circulation and hence to the maternal pulmonary arterial circulation,” the researchers said.

Strong uterine contractions are believed to raise the risk of amniotic fluid embolism, and induction and augmentation of labor have been proposed as possible contributing factors.

In their epidemiologic study of the association between drug-induced labor and amniotic fluid embolism, there were 180 cases of this condition, including 24 fatal cases, yielding a total rate of 6/100,000 singleton deliveries and a fatal rate of 0.8/100,000 singleton deliveries.

The rate was almost twice as high in women who had undergone medical induction of labor as in those who had not. This association remained robust after the data were adjusted to account for many other potential risk factors, such as maternal age, presentation, delivery method, previous cesarean delivery, pregnancy complications, and labor complications.

This finding “should be a cause for concern in view of the increasing tendency for clinicians to induce labour, and especially for routine induction at term or after term,” the investigators said.

They also found that multiple pregnancy, older maternal age, cesarean delivery, forceps- or vacuum-assisted delivery, eclampsia, polyhydramnios, placenta previa, placental abruption, cervical laceration, uterine rupture, and fetal distress all raised the risk of amniotic fluid embolism, though not to the degree that drug-induced labor did. Many of these risk factors could be directly related to “the presumed causal roles of strong uterine contractions, excess amniotic fluid, and disruption of the uterine vasculature,” the researchers noted.

Moreover, the link between amniotic embolism on the one hand and cesarean or instrumental vaginal delivery on the other “might simply reflect the difficult labours that led to these procedures, rather than true effects of the procedures themselves.”

In particular, “the very strong association with caesarean delivery could also indicate reverse causality (i.e., the caesarean could have been a consequence of the signs and symptoms of amniotic fluid embolism,” Dr. Kramer and his associates pointed out.

The rates of total and fatal amniotic fluid embolism did not increase over time in this study, even though the rate of medically induced labor did increase. This probably reflects the rarity of the disorder, or it could be because of the concomitant decrease in other risk factors, such as forceps delivery, they added.

Medical induction of labor appears to double the risk of amniotic fluid embolism, reported Dr. Michael S. Kramer of Montreal Children's Hospital and his associates.

Findings from their retrospective cohort study of approximately 3 million hospital births throughout Canada between 1991 and 2002 “support the long-standing, but heretofore unsubstantiated, suspicion that labour induction increases the risk of this rare but serious maternal complication.

“Although the small absolute risk of amniotic fluid embolism is unlikely to affect the decision to induce labour in the presence of compelling clinical indications, women and physicians should be aware of this risk if the decision is elective,” the researchers said in the Oct. 21 issue of the Lancet.

“We should emphasise that the absolute risk increase of amniotic fluid embolism for women undergoing medical induction of labour is very small: 4 or 5 total cases and 1 or 2 fatal cases per 100,000 women induced.

“However, with 4 million births per year and induction rates approaching 20% in the [United States], this practice could be causing amniotic fluid embolism in 30–40 women per year in the [United States] alone (including 10–15 deaths),” Dr. Kramer and his associates added (Lancet 2006;368:1444–8).

Despite being rare, amniotic fluid embolism is one of the leading causes of maternal mortality in developed countries, ahead of postpartum hemorrhage and other pulmonary embolisms. The cause of this catastrophic complication is not well understood. “It is thought to arise from a simultaneous tear in the fetal membranes and uterine vessels, through which amniotic fluid can pass into the uterine venous circulation and hence to the maternal pulmonary arterial circulation,” the researchers said.

Strong uterine contractions are believed to raise the risk of amniotic fluid embolism, and induction and augmentation of labor have been proposed as possible contributing factors.

In their epidemiologic study of the association between drug-induced labor and amniotic fluid embolism, there were 180 cases of this condition, including 24 fatal cases, yielding a total rate of 6/100,000 singleton deliveries and a fatal rate of 0.8/100,000 singleton deliveries.

The rate was almost twice as high in women who had undergone medical induction of labor as in those who had not. This association remained robust after the data were adjusted to account for many other potential risk factors, such as maternal age, presentation, delivery method, previous cesarean delivery, pregnancy complications, and labor complications.

This finding “should be a cause for concern in view of the increasing tendency for clinicians to induce labour, and especially for routine induction at term or after term,” the investigators said.

They also found that multiple pregnancy, older maternal age, cesarean delivery, forceps- or vacuum-assisted delivery, eclampsia, polyhydramnios, placenta previa, placental abruption, cervical laceration, uterine rupture, and fetal distress all raised the risk of amniotic fluid embolism, though not to the degree that drug-induced labor did. Many of these risk factors could be directly related to “the presumed causal roles of strong uterine contractions, excess amniotic fluid, and disruption of the uterine vasculature,” the researchers noted.

Moreover, the link between amniotic embolism on the one hand and cesarean or instrumental vaginal delivery on the other “might simply reflect the difficult labours that led to these procedures, rather than true effects of the procedures themselves.”

In particular, “the very strong association with caesarean delivery could also indicate reverse causality (i.e., the caesarean could have been a consequence of the signs and symptoms of amniotic fluid embolism,” Dr. Kramer and his associates pointed out.

The rates of total and fatal amniotic fluid embolism did not increase over time in this study, even though the rate of medically induced labor did increase. This probably reflects the rarity of the disorder, or it could be because of the concomitant decrease in other risk factors, such as forceps delivery, they added.

Islet transplantation using the Edmonton protocol restored long-term insulin production and glycemic stability in an international trial of 36 subjects with severe type 1 diabetes. However, the insulin independence that many of them initially achieved usually was not sustainable.

Nevertheless, even residual islet function without insulin independence still produced marked glycemic control and full protection from severe hypoglycemic episodes.

These results demonstrate that the Edmonton protocol for islet preparation and posttransplantation care is feasible and can be reproduced, although “normal endocrine reserve is rarely achieved, and insulin independence is gradually lost in most cases over time,” reported Dr. A.M. James Shapiro of the University of Alberta, Edmonton, and his associates.

The trial was conducted at six North American and three European medical centers. Each site followed four patients with diabetes of at least 5 years' duration who had failed on optimal insulin therapy with intensive glycemic monitoring. The subjects received up to three islet infusions and were followed for a mean of 41 months.

At 1 year post transplant, 16 of the 36 subjects (44%) had achieved glycemic control independent of insulin therapy, Dr. Shapiro and his associates said (N. Engl. J. Med. 2006;355:1318–30).

Another 10 subjects (28%) showed partial graft function, achieving complete protection from severe hypoglycemia and markedly improved glycemic control.

The remaining 10 subjects had complete graft loss and did not show clinical improvement. The graft never functioned in four of them and failed early in another two; the remaining four patients withdrew from treatment.

At 2-year follow-up, islet cell function had declined so that only 5 of the 16 subjects who had initially achieved insulin independence still retained it. The reason for this gradual loss is unknown, but one possible explanation is “metabolic exhaustion from chronic overstimulation of a marginal islet engraftment mass,” the investigators said.

There were 23 serious adverse events related to treatment, including reactions to immunosuppression in five patients and acute intraperitoneal bleeding from the procedure in seven. A “worrisome” decline in renal function was noted in some and was attributed to the combined toxic effects of immunosuppressive drugs on preexisting diabetic nephropathy.

“Islet transplantation may best be considered as an evolving therapy for use in highly selected patients with severe hypoglycemia or labile type 1 diabetes mellitus, provided all other attempts to stabilize glycemic control have been exhausted. For patients seeking long-term independence from insulin, whole-pancreas transplantation appears to offer more robust metabolic reserve at the present time,” they added.

In an editorial comment accompanying this report, Dr. Jonathan S. Bromberg and Dr. Derek LeRoith of the Mount Sinai School of Medicine, New York, said that the Edmonton protocol “is clearly orders of magnitude better than previous attempts at islet transplantation.”

However, the poor long-term results, high cost, and relatively high rate of major and minor adverse events “make it difficult to argue for expansion of islet transplantation to the general population,” they said (N. Engl. J. Med. 2006;355:1372–4).

Islet transplantation using the Edmonton protocol restored long-term insulin production and glycemic stability in an international trial of 36 subjects with severe type 1 diabetes. However, the insulin independence that many of them initially achieved usually was not sustainable.

Nevertheless, even residual islet function without insulin independence still produced marked glycemic control and full protection from severe hypoglycemic episodes.

These results demonstrate that the Edmonton protocol for islet preparation and posttransplantation care is feasible and can be reproduced, although “normal endocrine reserve is rarely achieved, and insulin independence is gradually lost in most cases over time,” reported Dr. A.M. James Shapiro of the University of Alberta, Edmonton, and his associates.

The trial was conducted at six North American and three European medical centers. Each site followed four patients with diabetes of at least 5 years' duration who had failed on optimal insulin therapy with intensive glycemic monitoring. The subjects received up to three islet infusions and were followed for a mean of 41 months.

At 1 year post transplant, 16 of the 36 subjects (44%) had achieved glycemic control independent of insulin therapy, Dr. Shapiro and his associates said (N. Engl. J. Med. 2006;355:1318–30).

Another 10 subjects (28%) showed partial graft function, achieving complete protection from severe hypoglycemia and markedly improved glycemic control.

The remaining 10 subjects had complete graft loss and did not show clinical improvement. The graft never functioned in four of them and failed early in another two; the remaining four patients withdrew from treatment.

At 2-year follow-up, islet cell function had declined so that only 5 of the 16 subjects who had initially achieved insulin independence still retained it. The reason for this gradual loss is unknown, but one possible explanation is “metabolic exhaustion from chronic overstimulation of a marginal islet engraftment mass,” the investigators said.

There were 23 serious adverse events related to treatment, including reactions to immunosuppression in five patients and acute intraperitoneal bleeding from the procedure in seven. A “worrisome” decline in renal function was noted in some and was attributed to the combined toxic effects of immunosuppressive drugs on preexisting diabetic nephropathy.

“Islet transplantation may best be considered as an evolving therapy for use in highly selected patients with severe hypoglycemia or labile type 1 diabetes mellitus, provided all other attempts to stabilize glycemic control have been exhausted. For patients seeking long-term independence from insulin, whole-pancreas transplantation appears to offer more robust metabolic reserve at the present time,” they added.

In an editorial comment accompanying this report, Dr. Jonathan S. Bromberg and Dr. Derek LeRoith of the Mount Sinai School of Medicine, New York, said that the Edmonton protocol “is clearly orders of magnitude better than previous attempts at islet transplantation.”

However, the poor long-term results, high cost, and relatively high rate of major and minor adverse events “make it difficult to argue for expansion of islet transplantation to the general population,” they said (N. Engl. J. Med. 2006;355:1372–4).

Islet transplantation using the Edmonton protocol restored long-term insulin production and glycemic stability in an international trial of 36 subjects with severe type 1 diabetes. However, the insulin independence that many of them initially achieved usually was not sustainable.

Nevertheless, even residual islet function without insulin independence still produced marked glycemic control and full protection from severe hypoglycemic episodes.

These results demonstrate that the Edmonton protocol for islet preparation and posttransplantation care is feasible and can be reproduced, although “normal endocrine reserve is rarely achieved, and insulin independence is gradually lost in most cases over time,” reported Dr. A.M. James Shapiro of the University of Alberta, Edmonton, and his associates.

The trial was conducted at six North American and three European medical centers. Each site followed four patients with diabetes of at least 5 years' duration who had failed on optimal insulin therapy with intensive glycemic monitoring. The subjects received up to three islet infusions and were followed for a mean of 41 months.

At 1 year post transplant, 16 of the 36 subjects (44%) had achieved glycemic control independent of insulin therapy, Dr. Shapiro and his associates said (N. Engl. J. Med. 2006;355:1318–30).

Another 10 subjects (28%) showed partial graft function, achieving complete protection from severe hypoglycemia and markedly improved glycemic control.

The remaining 10 subjects had complete graft loss and did not show clinical improvement. The graft never functioned in four of them and failed early in another two; the remaining four patients withdrew from treatment.

At 2-year follow-up, islet cell function had declined so that only 5 of the 16 subjects who had initially achieved insulin independence still retained it. The reason for this gradual loss is unknown, but one possible explanation is “metabolic exhaustion from chronic overstimulation of a marginal islet engraftment mass,” the investigators said.

There were 23 serious adverse events related to treatment, including reactions to immunosuppression in five patients and acute intraperitoneal bleeding from the procedure in seven. A “worrisome” decline in renal function was noted in some and was attributed to the combined toxic effects of immunosuppressive drugs on preexisting diabetic nephropathy.

“Islet transplantation may best be considered as an evolving therapy for use in highly selected patients with severe hypoglycemia or labile type 1 diabetes mellitus, provided all other attempts to stabilize glycemic control have been exhausted. For patients seeking long-term independence from insulin, whole-pancreas transplantation appears to offer more robust metabolic reserve at the present time,” they added.

In an editorial comment accompanying this report, Dr. Jonathan S. Bromberg and Dr. Derek LeRoith of the Mount Sinai School of Medicine, New York, said that the Edmonton protocol “is clearly orders of magnitude better than previous attempts at islet transplantation.”

However, the poor long-term results, high cost, and relatively high rate of major and minor adverse events “make it difficult to argue for expansion of islet transplantation to the general population,” they said (N. Engl. J. Med. 2006;355:1372–4).