Miriam E. Tucker

WASHINGTON — One-year data from a large, federally funded clinical trial have shown that intensive lifestyle intervention can produce significant weight loss and reduce cardiovascular risk factors among patients with type 2 diabetes, Dr. F. Xavier Pi-Sunyer reported at the annual scientific sessions of the American Diabetes Association.

The Look AHEAD (Action for Health in Diabetes) study is an ongoing 16-center randomized clinical trial designed to determine whether intensive lifestyle modification—including both decreased caloric intake and increased physical activity—can reduce the rates of both fatal and nonfatal myocardial infarctions and strokes in overweight volunteers with type 2 diabetes over a planned follow-up of 11.5 years, compared with traditional medical care.

The trial was funded primarily by the National Institutes of Health; other major donors include Federal Express, Health Management Resources, Johnson & Johnson, Lifescan Inc., Optifast-Novartis Nutrition, Roche Pharmaceuticals, Ross Products Division of Abbot Laboratories, and SlimFast Foods Company.

The study includes 5,145 patients with type 2 diabetes with a mean age of 59 and mean body mass index of 36 kg/m

The intensive lifestyle intervention (ILI), to which 2,570 patients were randomized, consisted of an initial 6-month phase in which they attended three group sessions and one individual session per month, all conducted by trained diabetes educators and emphasizing nutrition and physical activity aiming at a personal weight loss goal of 10% from baseline.

During months 7 through 12, subjects attended two or three sessions per month, either individually or in a group. Those who had achieved the first goal were aiming to maintain their weights, while those who hadn't continued to aim for the 10% loss.

Calorie recommendations were calculated based on baseline and goal weights, initially set at 1,200–1,500 kcal/day for those weighing 250 pounds or less at baseline and 1,500–1,800 kcal/day for those weighing more than 250 pounds. Participants could choose a regimen that included liquid meal replacements. Exercise was gradually increased to at least 25 minutes/day. Most participants walked, aiming for 10,000 daily steps, said Dr. Pi-Sunyer, director of the Obesity Research Center, St. Luke's-Roosevelt Hospital Center, New York.

The 2,575 control patients received diabetes support and education (DSE) consisting of three to four group meetings per year in which diet, exercise, and social support were discussed but no intervention was actually delivered, he said.

Of the 97% of study subjects who attended the 1-year exam, the ILI group had lost a mean of 8.3% of their body weight, compared with 0.4% in the controls, a highly significant difference. The average weight loss was about 18 pounds. The ILI group continued to lose weight for about the first 8 months of the study, after which their weight tended to plateau but did not rebound.

On average, the men lost about 3–4 pounds more than the women did. By race, whites lost a mean of 10% of their baseline body weight, compared with about 6.5% for Hispanics and African Americans and 6% among Native Americans. The 385 insulin users in the group lost a mean of 7% of their baseline body weight, and the 1,464 on oral antidiabetes medications lost 8%, whereas the 326 not taking any medications lost the most, with a mean of 9%.

Fitness, as measured by treadmill testing, improved by 16% in the ILI group and 11% in the controls, after adjustment for weight loss. Fitness improved significantly across all body mass indexes and in both genders and all the ethnic/minority groups. Changes in fitness were highly correlated with changes in activity level and in body weight, Dr. Pi-Sunyer noted.

Hemoglobin A_1c levels dropped from 7.25% at baseline to 6.6% at 1 year in the ILI group, a highly significant difference. In contrast, the drop from 7.3% to 7.15% in the DSE group was not significant.

Similarly, fasting glucose dropped by a mean of 21.5 mg/dL with ILI, compared with just 7.2 mg/dL in the DSE group. The improved hemoglobin A_1c occurred despite a greater reduction in glucose-lowering medications in the ILI group, he noted.

Systolic blood pressure dropped by 6.8 mm Hg in the ILI group vs. 2.8 mm Hg with DSE, and diastolic by 3.0 mm Hg vs. 1.8 mm Hg. Again, the reduction was significant only for ILI. Although LDL cholesterol levels didn't change significantly in either group, HDL cholesterol rose to a greater degree with ILI (3.4 vs. 1.4 mg/dL). Triglycerides dropped by 30.3 mg/dL with ILI, compared with just 14.6 mg/dL for DSE.

At 1 year, the ILI group was taking an average of 2.7 medications for glucose, blood pressure, and/or lipid lowering, compared with 3.2 for the DSE group, Dr. Pi-Sunyer reported.

“Continued intervention and follow-up will determine whether these changes will be maintained and lead to a reduction in cardiovascular events,” he said.

Triglycerides dropped by 30.3 mg/dL with the intervention group, compared with 14.6 mg/dL for the control. DR. PI-SUNYER

WASHINGTON — One-year data from a large, federally funded clinical trial have shown that intensive lifestyle intervention can produce significant weight loss and reduce cardiovascular risk factors among patients with type 2 diabetes, Dr. F. Xavier Pi-Sunyer reported at the annual scientific sessions of the American Diabetes Association.

The Look AHEAD (Action for Health in Diabetes) study is an ongoing 16-center randomized clinical trial designed to determine whether intensive lifestyle modification—including both decreased caloric intake and increased physical activity—can reduce the rates of both fatal and nonfatal myocardial infarctions and strokes in overweight volunteers with type 2 diabetes over a planned follow-up of 11.5 years, compared with traditional medical care.

The trial was funded primarily by the National Institutes of Health; other major donors include Federal Express, Health Management Resources, Johnson & Johnson, Lifescan Inc., Optifast-Novartis Nutrition, Roche Pharmaceuticals, Ross Products Division of Abbot Laboratories, and SlimFast Foods Company.

The study includes 5,145 patients with type 2 diabetes with a mean age of 59 and mean body mass index of 36 kg/m

The intensive lifestyle intervention (ILI), to which 2,570 patients were randomized, consisted of an initial 6-month phase in which they attended three group sessions and one individual session per month, all conducted by trained diabetes educators and emphasizing nutrition and physical activity aiming at a personal weight loss goal of 10% from baseline.

During months 7 through 12, subjects attended two or three sessions per month, either individually or in a group. Those who had achieved the first goal were aiming to maintain their weights, while those who hadn't continued to aim for the 10% loss.

Calorie recommendations were calculated based on baseline and goal weights, initially set at 1,200–1,500 kcal/day for those weighing 250 pounds or less at baseline and 1,500–1,800 kcal/day for those weighing more than 250 pounds. Participants could choose a regimen that included liquid meal replacements. Exercise was gradually increased to at least 25 minutes/day. Most participants walked, aiming for 10,000 daily steps, said Dr. Pi-Sunyer, director of the Obesity Research Center, St. Luke's-Roosevelt Hospital Center, New York.

The 2,575 control patients received diabetes support and education (DSE) consisting of three to four group meetings per year in which diet, exercise, and social support were discussed but no intervention was actually delivered, he said.

Of the 97% of study subjects who attended the 1-year exam, the ILI group had lost a mean of 8.3% of their body weight, compared with 0.4% in the controls, a highly significant difference. The average weight loss was about 18 pounds. The ILI group continued to lose weight for about the first 8 months of the study, after which their weight tended to plateau but did not rebound.

On average, the men lost about 3–4 pounds more than the women did. By race, whites lost a mean of 10% of their baseline body weight, compared with about 6.5% for Hispanics and African Americans and 6% among Native Americans. The 385 insulin users in the group lost a mean of 7% of their baseline body weight, and the 1,464 on oral antidiabetes medications lost 8%, whereas the 326 not taking any medications lost the most, with a mean of 9%.

Fitness, as measured by treadmill testing, improved by 16% in the ILI group and 11% in the controls, after adjustment for weight loss. Fitness improved significantly across all body mass indexes and in both genders and all the ethnic/minority groups. Changes in fitness were highly correlated with changes in activity level and in body weight, Dr. Pi-Sunyer noted.

Hemoglobin A_1c levels dropped from 7.25% at baseline to 6.6% at 1 year in the ILI group, a highly significant difference. In contrast, the drop from 7.3% to 7.15% in the DSE group was not significant.

Similarly, fasting glucose dropped by a mean of 21.5 mg/dL with ILI, compared with just 7.2 mg/dL in the DSE group. The improved hemoglobin A_1c occurred despite a greater reduction in glucose-lowering medications in the ILI group, he noted.

Systolic blood pressure dropped by 6.8 mm Hg in the ILI group vs. 2.8 mm Hg with DSE, and diastolic by 3.0 mm Hg vs. 1.8 mm Hg. Again, the reduction was significant only for ILI. Although LDL cholesterol levels didn't change significantly in either group, HDL cholesterol rose to a greater degree with ILI (3.4 vs. 1.4 mg/dL). Triglycerides dropped by 30.3 mg/dL with ILI, compared with just 14.6 mg/dL for DSE.

At 1 year, the ILI group was taking an average of 2.7 medications for glucose, blood pressure, and/or lipid lowering, compared with 3.2 for the DSE group, Dr. Pi-Sunyer reported.

“Continued intervention and follow-up will determine whether these changes will be maintained and lead to a reduction in cardiovascular events,” he said.

Triglycerides dropped by 30.3 mg/dL with the intervention group, compared with 14.6 mg/dL for the control. DR. PI-SUNYER

WASHINGTON — One-year data from a large, federally funded clinical trial have shown that intensive lifestyle intervention can produce significant weight loss and reduce cardiovascular risk factors among patients with type 2 diabetes, Dr. F. Xavier Pi-Sunyer reported at the annual scientific sessions of the American Diabetes Association.

The Look AHEAD (Action for Health in Diabetes) study is an ongoing 16-center randomized clinical trial designed to determine whether intensive lifestyle modification—including both decreased caloric intake and increased physical activity—can reduce the rates of both fatal and nonfatal myocardial infarctions and strokes in overweight volunteers with type 2 diabetes over a planned follow-up of 11.5 years, compared with traditional medical care.

The trial was funded primarily by the National Institutes of Health; other major donors include Federal Express, Health Management Resources, Johnson & Johnson, Lifescan Inc., Optifast-Novartis Nutrition, Roche Pharmaceuticals, Ross Products Division of Abbot Laboratories, and SlimFast Foods Company.

The study includes 5,145 patients with type 2 diabetes with a mean age of 59 and mean body mass index of 36 kg/m

The intensive lifestyle intervention (ILI), to which 2,570 patients were randomized, consisted of an initial 6-month phase in which they attended three group sessions and one individual session per month, all conducted by trained diabetes educators and emphasizing nutrition and physical activity aiming at a personal weight loss goal of 10% from baseline.

During months 7 through 12, subjects attended two or three sessions per month, either individually or in a group. Those who had achieved the first goal were aiming to maintain their weights, while those who hadn't continued to aim for the 10% loss.

Calorie recommendations were calculated based on baseline and goal weights, initially set at 1,200–1,500 kcal/day for those weighing 250 pounds or less at baseline and 1,500–1,800 kcal/day for those weighing more than 250 pounds. Participants could choose a regimen that included liquid meal replacements. Exercise was gradually increased to at least 25 minutes/day. Most participants walked, aiming for 10,000 daily steps, said Dr. Pi-Sunyer, director of the Obesity Research Center, St. Luke's-Roosevelt Hospital Center, New York.

The 2,575 control patients received diabetes support and education (DSE) consisting of three to four group meetings per year in which diet, exercise, and social support were discussed but no intervention was actually delivered, he said.

Of the 97% of study subjects who attended the 1-year exam, the ILI group had lost a mean of 8.3% of their body weight, compared with 0.4% in the controls, a highly significant difference. The average weight loss was about 18 pounds. The ILI group continued to lose weight for about the first 8 months of the study, after which their weight tended to plateau but did not rebound.

On average, the men lost about 3–4 pounds more than the women did. By race, whites lost a mean of 10% of their baseline body weight, compared with about 6.5% for Hispanics and African Americans and 6% among Native Americans. The 385 insulin users in the group lost a mean of 7% of their baseline body weight, and the 1,464 on oral antidiabetes medications lost 8%, whereas the 326 not taking any medications lost the most, with a mean of 9%.

Fitness, as measured by treadmill testing, improved by 16% in the ILI group and 11% in the controls, after adjustment for weight loss. Fitness improved significantly across all body mass indexes and in both genders and all the ethnic/minority groups. Changes in fitness were highly correlated with changes in activity level and in body weight, Dr. Pi-Sunyer noted.

Hemoglobin A_1c levels dropped from 7.25% at baseline to 6.6% at 1 year in the ILI group, a highly significant difference. In contrast, the drop from 7.3% to 7.15% in the DSE group was not significant.

Similarly, fasting glucose dropped by a mean of 21.5 mg/dL with ILI, compared with just 7.2 mg/dL in the DSE group. The improved hemoglobin A_1c occurred despite a greater reduction in glucose-lowering medications in the ILI group, he noted.

Systolic blood pressure dropped by 6.8 mm Hg in the ILI group vs. 2.8 mm Hg with DSE, and diastolic by 3.0 mm Hg vs. 1.8 mm Hg. Again, the reduction was significant only for ILI. Although LDL cholesterol levels didn't change significantly in either group, HDL cholesterol rose to a greater degree with ILI (3.4 vs. 1.4 mg/dL). Triglycerides dropped by 30.3 mg/dL with ILI, compared with just 14.6 mg/dL for DSE.

At 1 year, the ILI group was taking an average of 2.7 medications for glucose, blood pressure, and/or lipid lowering, compared with 3.2 for the DSE group, Dr. Pi-Sunyer reported.

“Continued intervention and follow-up will determine whether these changes will be maintained and lead to a reduction in cardiovascular events,” he said.

Triglycerides dropped by 30.3 mg/dL with the intervention group, compared with 14.6 mg/dL for the control. DR. PI-SUNYER

Hyperthermia appears safe and effective in the short term for the management of supraspinatus tendinopathy, Dr. Arrigo Giombini of the Italian National Olympic Committee, Rome, and associates reported.

There is currently no consensus about the treatment of choice for rotator cuff tendinopathy, a condition that affects about half of all athletes who impose repeated stress on their shoulders, such as swimmers and volleyball players. A variety of physical therapy modalities have been used to treat the condition, but few well-designed studies have evaluated their effectiveness, the investigators said (Am. J. Sports Med. 2006;34:1247–53).

Hyperthermia is becoming widely used in physical medicine and rehabilitation in central and southern Europe. This approach utilizes a machine that combines a superficial cooling system and a deep-heating source with a microwave power generator at 434 MHz. This frequency raises tissue to therapeutic temperatures to a depth of several centimeters into the skin with no risk of overheating the superficial tissues, Dr. Giombini and associates explained.

This study population, 29 male and 8 female athletes with a mean age of 27 years, all reported a gradual onset of shoulder pain that impaired their sports activities for 3–6 months despite nonoperative management, including nonsteroidal anti-inflammatory drugs and complete or modified rest from their sport.

The participants were randomized to receive treatment with either hyperthermia (14 subjects), ultrasound at 1 MHz (12 subjects), or exercise (11 subjects) for 4 weeks. The hyperthermia was delivered in 30-minute sessions three times a week, whereas the ultrasound treatments lasted 15 minutes each, also three times weekly. The exercise group performed passive shoulder exercises for 5 minutes, twice daily.

At the 6-week follow-up, only the hyperthermia group had significant reductions in pain scores on the visual analog scale, which ranges from 0 (no pain) to 10 (incredibly severe pain). Their mean VAS score dropped from 5.96 at study entry to 1.2 at 6 weeks, compared with insignificant reductions of 6.3 to 5.15 in the ultrasound group and 6.1 to 4.9 with passive exercise.

The hyperthermia group also showed significantly greater improvements on measures of resisted movement, painful arc, and Constant Morley functional assessment, an overall clinical assessment of the power of the subject's shoulder and his or her ability to perform normal tasks of daily living.

By the end of the study, 12 of the hyperthermia patients had returned to their chosen sports, compared with just 4 each of the ultrasound and exercise patients, Dr. Giombini and associates reported.

Four athletes in the study reported transient discomfort from the high temperature reached with hyperthermia, but treatment was not interrupted for that reason. There were no other adverse effects.

ELSEVIER GLOBAL MEDICAL NEWS

Hyperthermia appears safe and effective in the short term for the management of supraspinatus tendinopathy, Dr. Arrigo Giombini of the Italian National Olympic Committee, Rome, and associates reported.

There is currently no consensus about the treatment of choice for rotator cuff tendinopathy, a condition that affects about half of all athletes who impose repeated stress on their shoulders, such as swimmers and volleyball players. A variety of physical therapy modalities have been used to treat the condition, but few well-designed studies have evaluated their effectiveness, the investigators said (Am. J. Sports Med. 2006;34:1247–53).

Hyperthermia is becoming widely used in physical medicine and rehabilitation in central and southern Europe. This approach utilizes a machine that combines a superficial cooling system and a deep-heating source with a microwave power generator at 434 MHz. This frequency raises tissue to therapeutic temperatures to a depth of several centimeters into the skin with no risk of overheating the superficial tissues, Dr. Giombini and associates explained.

This study population, 29 male and 8 female athletes with a mean age of 27 years, all reported a gradual onset of shoulder pain that impaired their sports activities for 3–6 months despite nonoperative management, including nonsteroidal anti-inflammatory drugs and complete or modified rest from their sport.

The participants were randomized to receive treatment with either hyperthermia (14 subjects), ultrasound at 1 MHz (12 subjects), or exercise (11 subjects) for 4 weeks. The hyperthermia was delivered in 30-minute sessions three times a week, whereas the ultrasound treatments lasted 15 minutes each, also three times weekly. The exercise group performed passive shoulder exercises for 5 minutes, twice daily.

At the 6-week follow-up, only the hyperthermia group had significant reductions in pain scores on the visual analog scale, which ranges from 0 (no pain) to 10 (incredibly severe pain). Their mean VAS score dropped from 5.96 at study entry to 1.2 at 6 weeks, compared with insignificant reductions of 6.3 to 5.15 in the ultrasound group and 6.1 to 4.9 with passive exercise.

The hyperthermia group also showed significantly greater improvements on measures of resisted movement, painful arc, and Constant Morley functional assessment, an overall clinical assessment of the power of the subject's shoulder and his or her ability to perform normal tasks of daily living.

By the end of the study, 12 of the hyperthermia patients had returned to their chosen sports, compared with just 4 each of the ultrasound and exercise patients, Dr. Giombini and associates reported.

Four athletes in the study reported transient discomfort from the high temperature reached with hyperthermia, but treatment was not interrupted for that reason. There were no other adverse effects.

ELSEVIER GLOBAL MEDICAL NEWS

Hyperthermia appears safe and effective in the short term for the management of supraspinatus tendinopathy, Dr. Arrigo Giombini of the Italian National Olympic Committee, Rome, and associates reported.

There is currently no consensus about the treatment of choice for rotator cuff tendinopathy, a condition that affects about half of all athletes who impose repeated stress on their shoulders, such as swimmers and volleyball players. A variety of physical therapy modalities have been used to treat the condition, but few well-designed studies have evaluated their effectiveness, the investigators said (Am. J. Sports Med. 2006;34:1247–53).

Hyperthermia is becoming widely used in physical medicine and rehabilitation in central and southern Europe. This approach utilizes a machine that combines a superficial cooling system and a deep-heating source with a microwave power generator at 434 MHz. This frequency raises tissue to therapeutic temperatures to a depth of several centimeters into the skin with no risk of overheating the superficial tissues, Dr. Giombini and associates explained.

This study population, 29 male and 8 female athletes with a mean age of 27 years, all reported a gradual onset of shoulder pain that impaired their sports activities for 3–6 months despite nonoperative management, including nonsteroidal anti-inflammatory drugs and complete or modified rest from their sport.

The participants were randomized to receive treatment with either hyperthermia (14 subjects), ultrasound at 1 MHz (12 subjects), or exercise (11 subjects) for 4 weeks. The hyperthermia was delivered in 30-minute sessions three times a week, whereas the ultrasound treatments lasted 15 minutes each, also three times weekly. The exercise group performed passive shoulder exercises for 5 minutes, twice daily.

At the 6-week follow-up, only the hyperthermia group had significant reductions in pain scores on the visual analog scale, which ranges from 0 (no pain) to 10 (incredibly severe pain). Their mean VAS score dropped from 5.96 at study entry to 1.2 at 6 weeks, compared with insignificant reductions of 6.3 to 5.15 in the ultrasound group and 6.1 to 4.9 with passive exercise.

The hyperthermia group also showed significantly greater improvements on measures of resisted movement, painful arc, and Constant Morley functional assessment, an overall clinical assessment of the power of the subject's shoulder and his or her ability to perform normal tasks of daily living.

By the end of the study, 12 of the hyperthermia patients had returned to their chosen sports, compared with just 4 each of the ultrasound and exercise patients, Dr. Giombini and associates reported.

Four athletes in the study reported transient discomfort from the high temperature reached with hyperthermia, but treatment was not interrupted for that reason. There were no other adverse effects.

ELSEVIER GLOBAL MEDICAL NEWS

Use of the Air-Stirrup brace combined with an elastic wrap promotes a more rapid return to function following first-time grade I and II ankle sprains than do either one alone or other modes of treatment, reported Bruce D. Beynnon, Ph.D., of McClure Musculoskeletal Research Center, Burlington, Vt., and his associates.

For grade III sprains, however, treatment with either the Air-Stirrup brace or casting for 10 days followed by the use of an elastic wrap appears to produce comparable outcomes, according to the investigators (Am. J. Sports Med. 2006;34:1401–12).

In a study supported by Aircast Inc., 212 skeletally-mature patients with first-time ankle sprains were randomized depending on their sprain severity. The 64 with grade I injuries received either an elastic wrap (Ace), an Air-Stirrup ankle brace, or the wrap combined with the brace. The 116 patients with grade II ankle sprains received either an elastic wrap, Air-Stirrup ankle brace, the wrap combined with the brace, or a fiberglass walking cast worn for 10 days followed by the use of an elastic wrap. The 32 patients with grade III sprains were randomized to either Air-Stirrup ankle brace or a fiberglass walking cast worn for 10 days, and then followed by the use of an elastic wrap.

A total of 172 patients (52 grade I, 93 grade II, 27 grade III) completed all the analyses, including keeping a daily log at home. Among those with grade I sprains, it took less than half the time to return to normal walking with the combined treatment than with the individual modalities (4.62 days, compared with 11.16 with the elastic wrap alone and 10.33 with the Air-Stirrup brace alone). Return to normal stair climbing also showed a significant difference—more than twice as rapidly with the wrap plus brace as with the two solo treatments (5.46 vs. 12.05 and 11.43 days, respectively).

The patients with grade II ankle sprains who received the combined Air-Stirrup/elastic wrap required 10.1 days to return to normal walking and 11.72 days for normal stair climbing, compared with 11.67 and 13.38 days for the elastic wrap alone and 13.38/16.38 for the Air-Stirrup ankle brace alone. These differences were significant.

Also significant, function after casting—24.12 and 27.94 days for walking and stair climbing, respectively—was 40% longer than with the combined Air Stirrup/elastic wrap treatment, Dr. Beynnon and his associates reported.

For grade III ankle sprains, there was no difference between treatment with the Air-Stirrup brace and cast immobilization for 10 days followed by the use of elastic wrap until the return of normal walking or stair climbing (18.56 days for the Air-Stirrup versus 19 for casting for walking, 18.31 versus 21.08 for stair-climbing). It's possible that the combined treatment would have benefitted these patients—it wasn't studied because the numbers with grade III sprains were anticipated to be too small for meaningful comparison, the investigators explained.

Secondary outcome measures were less impressive. There was no difference between treatments among those with grade I sprains in time to return to walking with full weight bearing. The time required to regain full capability of normal activities of daily living did not differ among the treatments. Similar trends were seen with grade II sprains, although secondary outcomes were significantly better with the elastic wrap than with casting. No significant differences among the treatments were seen with grade III sprains.

There was no difference between treatments in time to return to walking with full weight bearing. DR. BEYNNON

Use of the Air-Stirrup brace combined with an elastic wrap promotes a more rapid return to function following first-time grade I and II ankle sprains than do either one alone or other modes of treatment, reported Bruce D. Beynnon, Ph.D., of McClure Musculoskeletal Research Center, Burlington, Vt., and his associates.

For grade III sprains, however, treatment with either the Air-Stirrup brace or casting for 10 days followed by the use of an elastic wrap appears to produce comparable outcomes, according to the investigators (Am. J. Sports Med. 2006;34:1401–12).

In a study supported by Aircast Inc., 212 skeletally-mature patients with first-time ankle sprains were randomized depending on their sprain severity. The 64 with grade I injuries received either an elastic wrap (Ace), an Air-Stirrup ankle brace, or the wrap combined with the brace. The 116 patients with grade II ankle sprains received either an elastic wrap, Air-Stirrup ankle brace, the wrap combined with the brace, or a fiberglass walking cast worn for 10 days followed by the use of an elastic wrap. The 32 patients with grade III sprains were randomized to either Air-Stirrup ankle brace or a fiberglass walking cast worn for 10 days, and then followed by the use of an elastic wrap.

A total of 172 patients (52 grade I, 93 grade II, 27 grade III) completed all the analyses, including keeping a daily log at home. Among those with grade I sprains, it took less than half the time to return to normal walking with the combined treatment than with the individual modalities (4.62 days, compared with 11.16 with the elastic wrap alone and 10.33 with the Air-Stirrup brace alone). Return to normal stair climbing also showed a significant difference—more than twice as rapidly with the wrap plus brace as with the two solo treatments (5.46 vs. 12.05 and 11.43 days, respectively).

The patients with grade II ankle sprains who received the combined Air-Stirrup/elastic wrap required 10.1 days to return to normal walking and 11.72 days for normal stair climbing, compared with 11.67 and 13.38 days for the elastic wrap alone and 13.38/16.38 for the Air-Stirrup ankle brace alone. These differences were significant.

Also significant, function after casting—24.12 and 27.94 days for walking and stair climbing, respectively—was 40% longer than with the combined Air Stirrup/elastic wrap treatment, Dr. Beynnon and his associates reported.

For grade III ankle sprains, there was no difference between treatment with the Air-Stirrup brace and cast immobilization for 10 days followed by the use of elastic wrap until the return of normal walking or stair climbing (18.56 days for the Air-Stirrup versus 19 for casting for walking, 18.31 versus 21.08 for stair-climbing). It's possible that the combined treatment would have benefitted these patients—it wasn't studied because the numbers with grade III sprains were anticipated to be too small for meaningful comparison, the investigators explained.

Secondary outcome measures were less impressive. There was no difference between treatments among those with grade I sprains in time to return to walking with full weight bearing. The time required to regain full capability of normal activities of daily living did not differ among the treatments. Similar trends were seen with grade II sprains, although secondary outcomes were significantly better with the elastic wrap than with casting. No significant differences among the treatments were seen with grade III sprains.

There was no difference between treatments in time to return to walking with full weight bearing. DR. BEYNNON

Use of the Air-Stirrup brace combined with an elastic wrap promotes a more rapid return to function following first-time grade I and II ankle sprains than do either one alone or other modes of treatment, reported Bruce D. Beynnon, Ph.D., of McClure Musculoskeletal Research Center, Burlington, Vt., and his associates.

For grade III sprains, however, treatment with either the Air-Stirrup brace or casting for 10 days followed by the use of an elastic wrap appears to produce comparable outcomes, according to the investigators (Am. J. Sports Med. 2006;34:1401–12).

In a study supported by Aircast Inc., 212 skeletally-mature patients with first-time ankle sprains were randomized depending on their sprain severity. The 64 with grade I injuries received either an elastic wrap (Ace), an Air-Stirrup ankle brace, or the wrap combined with the brace. The 116 patients with grade II ankle sprains received either an elastic wrap, Air-Stirrup ankle brace, the wrap combined with the brace, or a fiberglass walking cast worn for 10 days followed by the use of an elastic wrap. The 32 patients with grade III sprains were randomized to either Air-Stirrup ankle brace or a fiberglass walking cast worn for 10 days, and then followed by the use of an elastic wrap.

A total of 172 patients (52 grade I, 93 grade II, 27 grade III) completed all the analyses, including keeping a daily log at home. Among those with grade I sprains, it took less than half the time to return to normal walking with the combined treatment than with the individual modalities (4.62 days, compared with 11.16 with the elastic wrap alone and 10.33 with the Air-Stirrup brace alone). Return to normal stair climbing also showed a significant difference—more than twice as rapidly with the wrap plus brace as with the two solo treatments (5.46 vs. 12.05 and 11.43 days, respectively).

The patients with grade II ankle sprains who received the combined Air-Stirrup/elastic wrap required 10.1 days to return to normal walking and 11.72 days for normal stair climbing, compared with 11.67 and 13.38 days for the elastic wrap alone and 13.38/16.38 for the Air-Stirrup ankle brace alone. These differences were significant.

Also significant, function after casting—24.12 and 27.94 days for walking and stair climbing, respectively—was 40% longer than with the combined Air Stirrup/elastic wrap treatment, Dr. Beynnon and his associates reported.

For grade III ankle sprains, there was no difference between treatment with the Air-Stirrup brace and cast immobilization for 10 days followed by the use of elastic wrap until the return of normal walking or stair climbing (18.56 days for the Air-Stirrup versus 19 for casting for walking, 18.31 versus 21.08 for stair-climbing). It's possible that the combined treatment would have benefitted these patients—it wasn't studied because the numbers with grade III sprains were anticipated to be too small for meaningful comparison, the investigators explained.

Secondary outcome measures were less impressive. There was no difference between treatments among those with grade I sprains in time to return to walking with full weight bearing. The time required to regain full capability of normal activities of daily living did not differ among the treatments. Similar trends were seen with grade II sprains, although secondary outcomes were significantly better with the elastic wrap than with casting. No significant differences among the treatments were seen with grade III sprains.

There was no difference between treatments in time to return to walking with full weight bearing. DR. BEYNNON

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Data are limited, however, regarding its outcome in athletes who perform high-impact sports with marked mechanical demands, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months (minimum 2 years), 21 (66%) of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, however, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) were able to return to regular participation in their high-impact pivoting sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport.

Patients with lesions of 200 mm

No effect was seen for gender or lesion type on the athletes' ability to return to their high-impact sport.

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Data are limited, however, regarding its outcome in athletes who perform high-impact sports with marked mechanical demands, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months (minimum 2 years), 21 (66%) of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, however, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) were able to return to regular participation in their high-impact pivoting sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport.

Patients with lesions of 200 mm

No effect was seen for gender or lesion type on the athletes' ability to return to their high-impact sport.

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Data are limited, however, regarding its outcome in athletes who perform high-impact sports with marked mechanical demands, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months (minimum 2 years), 21 (66%) of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, however, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) were able to return to regular participation in their high-impact pivoting sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport.

Patients with lesions of 200 mm

No effect was seen for gender or lesion type on the athletes' ability to return to their high-impact sport.

Management of acne should involve combined treatment that targets as many of the underlying pathogenic factors as possible, according to new expert committee recommendations from the American Academy of Pediatrics.

The new document is adapted from a 2003 consensus report issued by an international group of dermatologists called the Global Alliance to Improve Outcomes in Acne. Their recommendations were based on evidence whenever possible, but also included expert opinion based on clinical experience (J. Am. Acad. Dermatol. 2003;49[suppl. 1]:S1–37).

That report was never published in the pediatric literature. The new AAP statement, which also includes data from articles published since 2003, “is essentially a reworking of the information for pediatricians,” said lead author Dr. Andrea L. Zaenglein, of the departments of dermatology and pediatrics at Pennsylvania State University, Hershey, in an interview.

Three basic principles underlie the recommendations, which were supported by an unrestricted educational grant from Galderma Laboratories L.P. (Pediatrics 2006 [Epub doi.10.1542/peds.2005–2022]):

▸ A topical retinoid should be the foundation of treatment for most patients with acne. Retinoids target the microcomedo, the precursor to all lesions. They are also comedolytic and have intrinsic anti-inflammatory effects, thus targeting two pathogenic factors in acne.

▸ Combining a topical retinoid with an antimicrobial agent targets three pathogenic factors. Clinical trials have shown that combination therapy results in significantly faster and greater clearing, as opposed to antimicrobial therapy alone.

▸ Oral antibiotics should be used only in moderate to severe acne and should not be used as monotherapy. They should be discontinued as soon as possible, usually within 8–12 weeks.

Depending on the degree of inflammation, topical retinoids may be used alone (when comedones predominate), or with an antimicrobial agent. Female patients also may benefit from hormonal therapy with oral contraceptives.

For severe acne, treatment with oral isotretinoin is recommended. Isotretinoin therapy should also be considered for cases of acne refractory to conventional therapy with a topical retinoid, benzoyl peroxide, and oral antibiotic therapy, Dr. Zaenglein and her associates said.

The central role of topical retinoids in treating both comedonal and inflammatory acne was new in the 2003 document. Before that, topical retinoids had been reserved primarily for patients with comedonal acne, the authors noted.

Because topical retinoids may cause burning and irritation, particularly during the early weeks of therapy, it's important to ask patients about the products they've tried previously and how well those were tolerated. The vehicle must be considered in the selection of a retinoid because some are more irritating than others. Alcohol-based gels are generally more irritating than are cream-based products, for example.

Educating the patient about starting off slowly—such as every second or third day—and using the medication for a shorter duration of contact (for example, by washing it off after a period of time) may improve compliance. Patients also should be warned not to use any concurrent over-the-counter medications, such as salicylic acid scrubs or astringents, which can increase irritation when used with a retinoid.

The three topical retinoids currently approved for use in the United States—tretinoin, adapalene, and tazarotene—decrease formation of microcomedos and subsequent acne lesions. The main difference is in cutaneous tolerability, which can vary among formulations. The document outlines the clinical data on each product.

Combination therapy—including a topical retinoid with either a topical or an oral antibiotic and benzoyl peroxide—is considered the standard of care for the majority of acne patients. Benefits include targeting different pathophysiologic factors, such as abnormal desquamation, proliferation of Propionibacterium acnes, and inflammation; increasing efficacy; improving the speed of lesion resolution; and minimizing the potential for antibiotic resistance, the authors said.

Antimicrobials were long considered a mainstay in the treatment of acne vulgaris. Now, in a climate of increasing antibiotic resistance, they are recommended as adjunctive rather than primary acne treatment. Topical antibiotics are indicated for mild inflammatory acne. They are typically well tolerated apart from occasional mild cutaneous irritation and burning. The topical macrolides erythromycin and clindamycin may be used alone or in combination with benzoyl peroxide.

Benzoyl peroxide is the most potent topical antimicrobial, with rapid bactericidal action. It is effective when used alone or combined with other antibiotics. It is available in many different formulations, including soaps, washes, creams, gels, and lotions, in concentrations of 1%–10%. Skin irritation is a common side effect, but it generally improves with time, they said.

Oral antibiotics should be reserved for patients with moderate to severe inflammatory acne. Tetracycline and the tetracycline derivatives doxycycline and minocycline are the most common agents; alternative choices include macrolides, cotrimoxazole, and trimethoprim. After improvement is noted, the oral antibiotic should be discontinued as soon as possible. If no improvement is seen within 8–16 weeks of initiation, a change in antibiotic is warranted because resistance is likely. When the patients stop oral therapy, they should continue with topical retinoid therapy to maintain improvement.

Oral contraceptives and spironolactone may be good options for managing acne in females who have sudden onset of severe acne, who have not responded to conventional first-line therapy, or who have persistent inflammatory papules and nodules involving primarily the lower face and neck. Hormonal therapies may be especially beneficial in female patients with hyperandrogenism, a need for birth control, or irregular menses.

Maintenance therapy should be initiated once clinical improvement is achieved, particularly in the young teenager in whom acne is likely to recur. Counseling is essential to the management of patients with acne, including assessing any adverse psychological effects of the condition, and dispelling myths (such as an acne-chocolate link), the authors advised.

Management of acne should involve combined treatment that targets as many of the underlying pathogenic factors as possible, according to new expert committee recommendations from the American Academy of Pediatrics.

The new document is adapted from a 2003 consensus report issued by an international group of dermatologists called the Global Alliance to Improve Outcomes in Acne. Their recommendations were based on evidence whenever possible, but also included expert opinion based on clinical experience (J. Am. Acad. Dermatol. 2003;49[suppl. 1]:S1–37).

That report was never published in the pediatric literature. The new AAP statement, which also includes data from articles published since 2003, “is essentially a reworking of the information for pediatricians,” said lead author Dr. Andrea L. Zaenglein, of the departments of dermatology and pediatrics at Pennsylvania State University, Hershey, in an interview.

Three basic principles underlie the recommendations, which were supported by an unrestricted educational grant from Galderma Laboratories L.P. (Pediatrics 2006 [Epub doi.10.1542/peds.2005–2022]):

▸ A topical retinoid should be the foundation of treatment for most patients with acne. Retinoids target the microcomedo, the precursor to all lesions. They are also comedolytic and have intrinsic anti-inflammatory effects, thus targeting two pathogenic factors in acne.

▸ Combining a topical retinoid with an antimicrobial agent targets three pathogenic factors. Clinical trials have shown that combination therapy results in significantly faster and greater clearing, as opposed to antimicrobial therapy alone.

▸ Oral antibiotics should be used only in moderate to severe acne and should not be used as monotherapy. They should be discontinued as soon as possible, usually within 8–12 weeks.

Depending on the degree of inflammation, topical retinoids may be used alone (when comedones predominate), or with an antimicrobial agent. Female patients also may benefit from hormonal therapy with oral contraceptives.

For severe acne, treatment with oral isotretinoin is recommended. Isotretinoin therapy should also be considered for cases of acne refractory to conventional therapy with a topical retinoid, benzoyl peroxide, and oral antibiotic therapy, Dr. Zaenglein and her associates said.

The central role of topical retinoids in treating both comedonal and inflammatory acne was new in the 2003 document. Before that, topical retinoids had been reserved primarily for patients with comedonal acne, the authors noted.

Because topical retinoids may cause burning and irritation, particularly during the early weeks of therapy, it's important to ask patients about the products they've tried previously and how well those were tolerated. The vehicle must be considered in the selection of a retinoid because some are more irritating than others. Alcohol-based gels are generally more irritating than are cream-based products, for example.

Educating the patient about starting off slowly—such as every second or third day—and using the medication for a shorter duration of contact (for example, by washing it off after a period of time) may improve compliance. Patients also should be warned not to use any concurrent over-the-counter medications, such as salicylic acid scrubs or astringents, which can increase irritation when used with a retinoid.

The three topical retinoids currently approved for use in the United States—tretinoin, adapalene, and tazarotene—decrease formation of microcomedos and subsequent acne lesions. The main difference is in cutaneous tolerability, which can vary among formulations. The document outlines the clinical data on each product.

Combination therapy—including a topical retinoid with either a topical or an oral antibiotic and benzoyl peroxide—is considered the standard of care for the majority of acne patients. Benefits include targeting different pathophysiologic factors, such as abnormal desquamation, proliferation of Propionibacterium acnes, and inflammation; increasing efficacy; improving the speed of lesion resolution; and minimizing the potential for antibiotic resistance, the authors said.

Antimicrobials were long considered a mainstay in the treatment of acne vulgaris. Now, in a climate of increasing antibiotic resistance, they are recommended as adjunctive rather than primary acne treatment. Topical antibiotics are indicated for mild inflammatory acne. They are typically well tolerated apart from occasional mild cutaneous irritation and burning. The topical macrolides erythromycin and clindamycin may be used alone or in combination with benzoyl peroxide.

Benzoyl peroxide is the most potent topical antimicrobial, with rapid bactericidal action. It is effective when used alone or combined with other antibiotics. It is available in many different formulations, including soaps, washes, creams, gels, and lotions, in concentrations of 1%–10%. Skin irritation is a common side effect, but it generally improves with time, they said.

Oral antibiotics should be reserved for patients with moderate to severe inflammatory acne. Tetracycline and the tetracycline derivatives doxycycline and minocycline are the most common agents; alternative choices include macrolides, cotrimoxazole, and trimethoprim. After improvement is noted, the oral antibiotic should be discontinued as soon as possible. If no improvement is seen within 8–16 weeks of initiation, a change in antibiotic is warranted because resistance is likely. When the patients stop oral therapy, they should continue with topical retinoid therapy to maintain improvement.

Oral contraceptives and spironolactone may be good options for managing acne in females who have sudden onset of severe acne, who have not responded to conventional first-line therapy, or who have persistent inflammatory papules and nodules involving primarily the lower face and neck. Hormonal therapies may be especially beneficial in female patients with hyperandrogenism, a need for birth control, or irregular menses.

Maintenance therapy should be initiated once clinical improvement is achieved, particularly in the young teenager in whom acne is likely to recur. Counseling is essential to the management of patients with acne, including assessing any adverse psychological effects of the condition, and dispelling myths (such as an acne-chocolate link), the authors advised.

Management of acne should involve combined treatment that targets as many of the underlying pathogenic factors as possible, according to new expert committee recommendations from the American Academy of Pediatrics.

The new document is adapted from a 2003 consensus report issued by an international group of dermatologists called the Global Alliance to Improve Outcomes in Acne. Their recommendations were based on evidence whenever possible, but also included expert opinion based on clinical experience (J. Am. Acad. Dermatol. 2003;49[suppl. 1]:S1–37).

That report was never published in the pediatric literature. The new AAP statement, which also includes data from articles published since 2003, “is essentially a reworking of the information for pediatricians,” said lead author Dr. Andrea L. Zaenglein, of the departments of dermatology and pediatrics at Pennsylvania State University, Hershey, in an interview.

Three basic principles underlie the recommendations, which were supported by an unrestricted educational grant from Galderma Laboratories L.P. (Pediatrics 2006 [Epub doi.10.1542/peds.2005–2022]):

▸ A topical retinoid should be the foundation of treatment for most patients with acne. Retinoids target the microcomedo, the precursor to all lesions. They are also comedolytic and have intrinsic anti-inflammatory effects, thus targeting two pathogenic factors in acne.

▸ Combining a topical retinoid with an antimicrobial agent targets three pathogenic factors. Clinical trials have shown that combination therapy results in significantly faster and greater clearing, as opposed to antimicrobial therapy alone.

▸ Oral antibiotics should be used only in moderate to severe acne and should not be used as monotherapy. They should be discontinued as soon as possible, usually within 8–12 weeks.

Depending on the degree of inflammation, topical retinoids may be used alone (when comedones predominate), or with an antimicrobial agent. Female patients also may benefit from hormonal therapy with oral contraceptives.

For severe acne, treatment with oral isotretinoin is recommended. Isotretinoin therapy should also be considered for cases of acne refractory to conventional therapy with a topical retinoid, benzoyl peroxide, and oral antibiotic therapy, Dr. Zaenglein and her associates said.

The central role of topical retinoids in treating both comedonal and inflammatory acne was new in the 2003 document. Before that, topical retinoids had been reserved primarily for patients with comedonal acne, the authors noted.

Because topical retinoids may cause burning and irritation, particularly during the early weeks of therapy, it's important to ask patients about the products they've tried previously and how well those were tolerated. The vehicle must be considered in the selection of a retinoid because some are more irritating than others. Alcohol-based gels are generally more irritating than are cream-based products, for example.

Educating the patient about starting off slowly—such as every second or third day—and using the medication for a shorter duration of contact (for example, by washing it off after a period of time) may improve compliance. Patients also should be warned not to use any concurrent over-the-counter medications, such as salicylic acid scrubs or astringents, which can increase irritation when used with a retinoid.

The three topical retinoids currently approved for use in the United States—tretinoin, adapalene, and tazarotene—decrease formation of microcomedos and subsequent acne lesions. The main difference is in cutaneous tolerability, which can vary among formulations. The document outlines the clinical data on each product.

Combination therapy—including a topical retinoid with either a topical or an oral antibiotic and benzoyl peroxide—is considered the standard of care for the majority of acne patients. Benefits include targeting different pathophysiologic factors, such as abnormal desquamation, proliferation of Propionibacterium acnes, and inflammation; increasing efficacy; improving the speed of lesion resolution; and minimizing the potential for antibiotic resistance, the authors said.

Antimicrobials were long considered a mainstay in the treatment of acne vulgaris. Now, in a climate of increasing antibiotic resistance, they are recommended as adjunctive rather than primary acne treatment. Topical antibiotics are indicated for mild inflammatory acne. They are typically well tolerated apart from occasional mild cutaneous irritation and burning. The topical macrolides erythromycin and clindamycin may be used alone or in combination with benzoyl peroxide.

Benzoyl peroxide is the most potent topical antimicrobial, with rapid bactericidal action. It is effective when used alone or combined with other antibiotics. It is available in many different formulations, including soaps, washes, creams, gels, and lotions, in concentrations of 1%–10%. Skin irritation is a common side effect, but it generally improves with time, they said.

Oral antibiotics should be reserved for patients with moderate to severe inflammatory acne. Tetracycline and the tetracycline derivatives doxycycline and minocycline are the most common agents; alternative choices include macrolides, cotrimoxazole, and trimethoprim. After improvement is noted, the oral antibiotic should be discontinued as soon as possible. If no improvement is seen within 8–16 weeks of initiation, a change in antibiotic is warranted because resistance is likely. When the patients stop oral therapy, they should continue with topical retinoid therapy to maintain improvement.

Oral contraceptives and spironolactone may be good options for managing acne in females who have sudden onset of severe acne, who have not responded to conventional first-line therapy, or who have persistent inflammatory papules and nodules involving primarily the lower face and neck. Hormonal therapies may be especially beneficial in female patients with hyperandrogenism, a need for birth control, or irregular menses.

Maintenance therapy should be initiated once clinical improvement is achieved, particularly in the young teenager in whom acne is likely to recur. Counseling is essential to the management of patients with acne, including assessing any adverse psychological effects of the condition, and dispelling myths (such as an acne-chocolate link), the authors advised.

Fluoroquinolone use in children should be restricted to situations in which there is no safe and effective alternative either for treating an infection caused by multidrug resistant bacteria or in which parenteral therapy is not feasible.

The recommendations, released in a new policy statement from the American Academy of Pediatrics' Committee on Infectious Disease (COID), are in response both to concerns about increasing rates of bacterial resistance and to the potential association of fluoroquinolones with adverse musculoskeletal events (Pediatrics;doi:10.1542/peds.2006-1772).

“The COID felt that the use of fluoroquinolones in children was not necessary in most situations, and we wanted to be very specific about how they should be used,” lead author and former COID chair Dr. Keith R. Powell said in an interview.

The committee advises that appropriate use be limited to the following specific scenarios:

▸ Exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease (Food and Drug Administration licensed use).

▸ Urinary tract infections caused by Pseudomonas aeruginosa or other multidrug-resistant, gram-negative bacteria (FDA licensed for complicated Escherichia coli urinary tract infections and pyelonephritis attributable to E. coli in patients 1–17 years of age).

▸ Chronic suppurative otitis media or malignant otitis externa caused by P. aeruginosa.

▸ Chronic or acute osteomyelitis or osteochondritis caused by P. aeruginosa (not for prophylaxis for nail puncture wounds to the foot).

▸ Exacerbation of pulmonary disease in patients with cystic fibrosis who have colonization with P. aeruginosa and who can be treated in an ambulatory setting.

▸ Mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones.

▸ Gram-negative bacterial infections in immunocompromised hosts in whom oral therapy is desired or resistance to alternative agents is present.

▸ Gastrointestinal tract infection caused by multidrug-resistant Shigella species, Salmonella species, Vibrio cholerae, or Campylobacter jejuni.

▸ Documented bacterial septicemia or meningitis attributable to organisms with in vitro resistance to approved agents or in immunocompromised infants and children who have failed to respond to parenteral therapy with other appropriate antimicrobial agents.

▸ Serious infections attributable to fluoroquinolone-susceptible pathogen(s) in children with life-threatening allergy to alternative agents.

For many years, fluoroquinolones had been contraindicated in children because animal data suggested that the antimicrobials may cause joint toxicity.

Prior to 2004, ciprofloxacin was the only fluoroquinolone licensed for use in children less than 18 years of age, and only for inhalational anthrax. That year, the FDA approved ciprofloxacin for treating complicated urinary tract infections and pyelonephritis caused by E. coli in patients aged 1–17 years.

But despite the fact that inhalational anthrax was the only approved use of fluoroquinolones in children prior to 2004, U.S. pharmacy sales and distribution data from 2002 indicate that there were approximately 520,000 fluoroquinolone prescriptions written for children and adolescents younger than 18 years. Approximately 13,800 of those prescriptions were written for children aged 2–6 years, and 2,750 were written for infants younger than 2 years of age.

There has been no decrease in prescribing for children since 2002, COID member Dr. John S. Bradley said.

The increased use of fluoroquinolones in all age groups has resulted in a corresponding increase in bacterial resistance to these agents. One study in adults with cystic fibrosis demonstrated that the proportion of susceptible P. aeruginosa isolates decreased from 100% to 45% after 14 days of treatment (Am. J. Med. 1987;82:189–95).

Fluoroquinolone resistance in Streptococcus pneumoniae also has been increasing. Susceptibility testing of 5,640 S. pneumoniae strains isolated during the 1997–1998 respiratory illness season from 377 hospitals in the United States showed only 0.3% of isolates to be resistant to ciprofloxacin. In contrast, among isolates obtained from January 1999 through August 2000, 3% were resistant to ciprofloxacin, 0.5% to levofloxacin, and 0.4% to gatifloxacin (Diagn. Microbiol. Infect. Dis. 2002;43:207–17).

Concurrent with the overprescribing and increasing resistance are data showing that fluoroquinolones have been associated with arthropathy in children. Ciprofloxacin labeling by the FDA includes data regarding musculoskeletal adverse events in children aged 1–17 years who received the drug to treat complicated E. coli urinary tract infections and pyelonephritis attributable to E. coli. Compared with a rate of 6.0% (21/349) at 6 weeks among controls, musculoskeletal adverse events occurred in 9.3% (31/335) of children within 6 weeks of receiving ciprofloxacin. Most of these events associated with fluoroquinolones were transient and of moderate intensity.

None of the published studies reviewed for the AAP document showed a statistically significant increase in arthropathies, although there is a trend for mild to moderate events, noted Dr. Bradley, director of the division of infectious diseases at Children's Hospital and Health Center, San Diego.

The COID concluded that the use of a fluoroquinolone in a child or adolescent may be justified in special circumstances, after careful assessment of the risks and benefits for the individual patient. Although there is no compelling evidence linking fluoroquinolones with sustained injury to developing joints in humans, the possibility that this may occur infrequently has not been excluded, Dr. Powell and his associates said.

Fluoroquinolone use in children should be restricted to situations in which there is no safe and effective alternative either for treating an infection caused by multidrug resistant bacteria or in which parenteral therapy is not feasible.

The recommendations, released in a new policy statement from the American Academy of Pediatrics' Committee on Infectious Disease (COID), are in response both to concerns about increasing rates of bacterial resistance and to the potential association of fluoroquinolones with adverse musculoskeletal events (Pediatrics;doi:10.1542/peds.2006-1772).

“The COID felt that the use of fluoroquinolones in children was not necessary in most situations, and we wanted to be very specific about how they should be used,” lead author and former COID chair Dr. Keith R. Powell said in an interview.

The committee advises that appropriate use be limited to the following specific scenarios:

▸ Exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease (Food and Drug Administration licensed use).

▸ Urinary tract infections caused by Pseudomonas aeruginosa or other multidrug-resistant, gram-negative bacteria (FDA licensed for complicated Escherichia coli urinary tract infections and pyelonephritis attributable to E. coli in patients 1–17 years of age).

▸ Chronic suppurative otitis media or malignant otitis externa caused by P. aeruginosa.

▸ Chronic or acute osteomyelitis or osteochondritis caused by P. aeruginosa (not for prophylaxis for nail puncture wounds to the foot).

▸ Exacerbation of pulmonary disease in patients with cystic fibrosis who have colonization with P. aeruginosa and who can be treated in an ambulatory setting.

▸ Mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones.

▸ Gram-negative bacterial infections in immunocompromised hosts in whom oral therapy is desired or resistance to alternative agents is present.

▸ Gastrointestinal tract infection caused by multidrug-resistant Shigella species, Salmonella species, Vibrio cholerae, or Campylobacter jejuni.

▸ Documented bacterial septicemia or meningitis attributable to organisms with in vitro resistance to approved agents or in immunocompromised infants and children who have failed to respond to parenteral therapy with other appropriate antimicrobial agents.

▸ Serious infections attributable to fluoroquinolone-susceptible pathogen(s) in children with life-threatening allergy to alternative agents.

For many years, fluoroquinolones had been contraindicated in children because animal data suggested that the antimicrobials may cause joint toxicity.

Prior to 2004, ciprofloxacin was the only fluoroquinolone licensed for use in children less than 18 years of age, and only for inhalational anthrax. That year, the FDA approved ciprofloxacin for treating complicated urinary tract infections and pyelonephritis caused by E. coli in patients aged 1–17 years.

But despite the fact that inhalational anthrax was the only approved use of fluoroquinolones in children prior to 2004, U.S. pharmacy sales and distribution data from 2002 indicate that there were approximately 520,000 fluoroquinolone prescriptions written for children and adolescents younger than 18 years. Approximately 13,800 of those prescriptions were written for children aged 2–6 years, and 2,750 were written for infants younger than 2 years of age.

There has been no decrease in prescribing for children since 2002, COID member Dr. John S. Bradley said.

The increased use of fluoroquinolones in all age groups has resulted in a corresponding increase in bacterial resistance to these agents. One study in adults with cystic fibrosis demonstrated that the proportion of susceptible P. aeruginosa isolates decreased from 100% to 45% after 14 days of treatment (Am. J. Med. 1987;82:189–95).

Fluoroquinolone resistance in Streptococcus pneumoniae also has been increasing. Susceptibility testing of 5,640 S. pneumoniae strains isolated during the 1997–1998 respiratory illness season from 377 hospitals in the United States showed only 0.3% of isolates to be resistant to ciprofloxacin. In contrast, among isolates obtained from January 1999 through August 2000, 3% were resistant to ciprofloxacin, 0.5% to levofloxacin, and 0.4% to gatifloxacin (Diagn. Microbiol. Infect. Dis. 2002;43:207–17).

Concurrent with the overprescribing and increasing resistance are data showing that fluoroquinolones have been associated with arthropathy in children. Ciprofloxacin labeling by the FDA includes data regarding musculoskeletal adverse events in children aged 1–17 years who received the drug to treat complicated E. coli urinary tract infections and pyelonephritis attributable to E. coli. Compared with a rate of 6.0% (21/349) at 6 weeks among controls, musculoskeletal adverse events occurred in 9.3% (31/335) of children within 6 weeks of receiving ciprofloxacin. Most of these events associated with fluoroquinolones were transient and of moderate intensity.

None of the published studies reviewed for the AAP document showed a statistically significant increase in arthropathies, although there is a trend for mild to moderate events, noted Dr. Bradley, director of the division of infectious diseases at Children's Hospital and Health Center, San Diego.

The COID concluded that the use of a fluoroquinolone in a child or adolescent may be justified in special circumstances, after careful assessment of the risks and benefits for the individual patient. Although there is no compelling evidence linking fluoroquinolones with sustained injury to developing joints in humans, the possibility that this may occur infrequently has not been excluded, Dr. Powell and his associates said.

Fluoroquinolone use in children should be restricted to situations in which there is no safe and effective alternative either for treating an infection caused by multidrug resistant bacteria or in which parenteral therapy is not feasible.

The recommendations, released in a new policy statement from the American Academy of Pediatrics' Committee on Infectious Disease (COID), are in response both to concerns about increasing rates of bacterial resistance and to the potential association of fluoroquinolones with adverse musculoskeletal events (Pediatrics;doi:10.1542/peds.2006-1772).

“The COID felt that the use of fluoroquinolones in children was not necessary in most situations, and we wanted to be very specific about how they should be used,” lead author and former COID chair Dr. Keith R. Powell said in an interview.

The committee advises that appropriate use be limited to the following specific scenarios:

▸ Exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease (Food and Drug Administration licensed use).

▸ Urinary tract infections caused by Pseudomonas aeruginosa or other multidrug-resistant, gram-negative bacteria (FDA licensed for complicated Escherichia coli urinary tract infections and pyelonephritis attributable to E. coli in patients 1–17 years of age).

▸ Chronic suppurative otitis media or malignant otitis externa caused by P. aeruginosa.

▸ Chronic or acute osteomyelitis or osteochondritis caused by P. aeruginosa (not for prophylaxis for nail puncture wounds to the foot).

▸ Exacerbation of pulmonary disease in patients with cystic fibrosis who have colonization with P. aeruginosa and who can be treated in an ambulatory setting.

▸ Mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones.

▸ Gram-negative bacterial infections in immunocompromised hosts in whom oral therapy is desired or resistance to alternative agents is present.

▸ Gastrointestinal tract infection caused by multidrug-resistant Shigella species, Salmonella species, Vibrio cholerae, or Campylobacter jejuni.

▸ Documented bacterial septicemia or meningitis attributable to organisms with in vitro resistance to approved agents or in immunocompromised infants and children who have failed to respond to parenteral therapy with other appropriate antimicrobial agents.

▸ Serious infections attributable to fluoroquinolone-susceptible pathogen(s) in children with life-threatening allergy to alternative agents.

For many years, fluoroquinolones had been contraindicated in children because animal data suggested that the antimicrobials may cause joint toxicity.

Prior to 2004, ciprofloxacin was the only fluoroquinolone licensed for use in children less than 18 years of age, and only for inhalational anthrax. That year, the FDA approved ciprofloxacin for treating complicated urinary tract infections and pyelonephritis caused by E. coli in patients aged 1–17 years.

But despite the fact that inhalational anthrax was the only approved use of fluoroquinolones in children prior to 2004, U.S. pharmacy sales and distribution data from 2002 indicate that there were approximately 520,000 fluoroquinolone prescriptions written for children and adolescents younger than 18 years. Approximately 13,800 of those prescriptions were written for children aged 2–6 years, and 2,750 were written for infants younger than 2 years of age.

There has been no decrease in prescribing for children since 2002, COID member Dr. John S. Bradley said.

The increased use of fluoroquinolones in all age groups has resulted in a corresponding increase in bacterial resistance to these agents. One study in adults with cystic fibrosis demonstrated that the proportion of susceptible P. aeruginosa isolates decreased from 100% to 45% after 14 days of treatment (Am. J. Med. 1987;82:189–95).

Fluoroquinolone resistance in Streptococcus pneumoniae also has been increasing. Susceptibility testing of 5,640 S. pneumoniae strains isolated during the 1997–1998 respiratory illness season from 377 hospitals in the United States showed only 0.3% of isolates to be resistant to ciprofloxacin. In contrast, among isolates obtained from January 1999 through August 2000, 3% were resistant to ciprofloxacin, 0.5% to levofloxacin, and 0.4% to gatifloxacin (Diagn. Microbiol. Infect. Dis. 2002;43:207–17).

Concurrent with the overprescribing and increasing resistance are data showing that fluoroquinolones have been associated with arthropathy in children. Ciprofloxacin labeling by the FDA includes data regarding musculoskeletal adverse events in children aged 1–17 years who received the drug to treat complicated E. coli urinary tract infections and pyelonephritis attributable to E. coli. Compared with a rate of 6.0% (21/349) at 6 weeks among controls, musculoskeletal adverse events occurred in 9.3% (31/335) of children within 6 weeks of receiving ciprofloxacin. Most of these events associated with fluoroquinolones were transient and of moderate intensity.

None of the published studies reviewed for the AAP document showed a statistically significant increase in arthropathies, although there is a trend for mild to moderate events, noted Dr. Bradley, director of the division of infectious diseases at Children's Hospital and Health Center, San Diego.

The COID concluded that the use of a fluoroquinolone in a child or adolescent may be justified in special circumstances, after careful assessment of the risks and benefits for the individual patient. Although there is no compelling evidence linking fluoroquinolones with sustained injury to developing joints in humans, the possibility that this may occur infrequently has not been excluded, Dr. Powell and his associates said.

WASHINGTON — People of all ages with type 2 diabetes are at increased risk for essential hypertension, but the relationship is exceptionally strong in children and adolescents, Dr. Scott J. Jacober and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

Essential hypertension and type 2 diabetes often coexist, but this retrospective study of a nationwide electronic medical records database is believed to be the first to examine the prevalence of essential hypertension by age group in individuals with and without diabetes, said Dr. Jacober, who was with Lilly Research Laboratories, Indianapolis, at the time of the study.

The database contained more than 4 million patients, and the study population, from 49 states during 1996–2005, comprised 231,492 individuals with a physician's diagnosis of type 2 diabetes; patients with type 1 diabetes were excluded. The study also included 1,219,047 people without type 2 diabetes. Overall, essential hypertension was diagnosed in 63% of patients with type 2 diabetes, compared with 40% of those without.

The difference was striking in children younger than age 12 years. Essential hypertension was present in 26.3% of the 219 with type 2 diabetes, compared with 0.5% of the 49,984 without, for an unadjusted odds ratio of 56.1.

Even after adjustment for age, gender, geographic region, and five comorbid conditions (obesity, hyperlipidemia, nephritis, ischemic heart disease, and other forms of heart disease), children aged 0–11 years with type 2 diabetes still were more than 20 times more likely than those without to have essential hypertension, Dr. Jacober and his colleagues reported.

Among adolescents aged 12–19 years, essential hypertension was present in 9.7% of the 691 with type 2 diabetes vs. 1.8% of the 61,129 without. In this age group, the unadjusted odds ratio was 4.4 and the adjusted odds ratio was 2.3, also highly significant.

Differences were less dramatic among adults, but still were statistically significant for all age groups even after adjustment. Among the 2,808 young adults aged 20–29, essential hypertension was present in 21% of those with type 2 diabetes vs. 7.3% of those without, with a 50% increased risk for essential hypertension after adjustment.

Overall, the prevalence of essential hypertension among the diabetics increased by decade of life from 36% at ages 30–39 to 70% at ages 70–79, dropping slightly thereafter to 67% among people over 80 years of age. Among the nondiabetics, essential hypertension was present in 19.5% of the 30- to 39-year-olds, rising to 60% for those aged 70–79, and again dropping slightly thereafter to 58%.

WASHINGTON — People of all ages with type 2 diabetes are at increased risk for essential hypertension, but the relationship is exceptionally strong in children and adolescents, Dr. Scott J. Jacober and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

Essential hypertension and type 2 diabetes often coexist, but this retrospective study of a nationwide electronic medical records database is believed to be the first to examine the prevalence of essential hypertension by age group in individuals with and without diabetes, said Dr. Jacober, who was with Lilly Research Laboratories, Indianapolis, at the time of the study.

The database contained more than 4 million patients, and the study population, from 49 states during 1996–2005, comprised 231,492 individuals with a physician's diagnosis of type 2 diabetes; patients with type 1 diabetes were excluded. The study also included 1,219,047 people without type 2 diabetes. Overall, essential hypertension was diagnosed in 63% of patients with type 2 diabetes, compared with 40% of those without.

The difference was striking in children younger than age 12 years. Essential hypertension was present in 26.3% of the 219 with type 2 diabetes, compared with 0.5% of the 49,984 without, for an unadjusted odds ratio of 56.1.

Even after adjustment for age, gender, geographic region, and five comorbid conditions (obesity, hyperlipidemia, nephritis, ischemic heart disease, and other forms of heart disease), children aged 0–11 years with type 2 diabetes still were more than 20 times more likely than those without to have essential hypertension, Dr. Jacober and his colleagues reported.

Among adolescents aged 12–19 years, essential hypertension was present in 9.7% of the 691 with type 2 diabetes vs. 1.8% of the 61,129 without. In this age group, the unadjusted odds ratio was 4.4 and the adjusted odds ratio was 2.3, also highly significant.

Differences were less dramatic among adults, but still were statistically significant for all age groups even after adjustment. Among the 2,808 young adults aged 20–29, essential hypertension was present in 21% of those with type 2 diabetes vs. 7.3% of those without, with a 50% increased risk for essential hypertension after adjustment.

Overall, the prevalence of essential hypertension among the diabetics increased by decade of life from 36% at ages 30–39 to 70% at ages 70–79, dropping slightly thereafter to 67% among people over 80 years of age. Among the nondiabetics, essential hypertension was present in 19.5% of the 30- to 39-year-olds, rising to 60% for those aged 70–79, and again dropping slightly thereafter to 58%.

WASHINGTON — People of all ages with type 2 diabetes are at increased risk for essential hypertension, but the relationship is exceptionally strong in children and adolescents, Dr. Scott J. Jacober and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

Essential hypertension and type 2 diabetes often coexist, but this retrospective study of a nationwide electronic medical records database is believed to be the first to examine the prevalence of essential hypertension by age group in individuals with and without diabetes, said Dr. Jacober, who was with Lilly Research Laboratories, Indianapolis, at the time of the study.

The database contained more than 4 million patients, and the study population, from 49 states during 1996–2005, comprised 231,492 individuals with a physician's diagnosis of type 2 diabetes; patients with type 1 diabetes were excluded. The study also included 1,219,047 people without type 2 diabetes. Overall, essential hypertension was diagnosed in 63% of patients with type 2 diabetes, compared with 40% of those without.

The difference was striking in children younger than age 12 years. Essential hypertension was present in 26.3% of the 219 with type 2 diabetes, compared with 0.5% of the 49,984 without, for an unadjusted odds ratio of 56.1.

Even after adjustment for age, gender, geographic region, and five comorbid conditions (obesity, hyperlipidemia, nephritis, ischemic heart disease, and other forms of heart disease), children aged 0–11 years with type 2 diabetes still were more than 20 times more likely than those without to have essential hypertension, Dr. Jacober and his colleagues reported.

Among adolescents aged 12–19 years, essential hypertension was present in 9.7% of the 691 with type 2 diabetes vs. 1.8% of the 61,129 without. In this age group, the unadjusted odds ratio was 4.4 and the adjusted odds ratio was 2.3, also highly significant.

Differences were less dramatic among adults, but still were statistically significant for all age groups even after adjustment. Among the 2,808 young adults aged 20–29, essential hypertension was present in 21% of those with type 2 diabetes vs. 7.3% of those without, with a 50% increased risk for essential hypertension after adjustment.

Overall, the prevalence of essential hypertension among the diabetics increased by decade of life from 36% at ages 30–39 to 70% at ages 70–79, dropping slightly thereafter to 67% among people over 80 years of age. Among the nondiabetics, essential hypertension was present in 19.5% of the 30- to 39-year-olds, rising to 60% for those aged 70–79, and again dropping slightly thereafter to 58%.

LUCAYA, BAHAMAS — Partial closure is an underutilized technique that can improve the outcome of surgical reconstruction after Mohs surgery for many patients, Dr. J. Robert Hamill Jr. said at a meeting of the American Society for Mohs Surgery.

Indeed, closing only part of the wound and leaving the rest to granulate on its own is advantageous in a wide variety of situations. Surgical sites to consider for partial closure include:

▸ Tumor sites that need to be monitored for recurrence.

▸ Surgical sites under high tension, including the leg, scalp, and fingers.

▸ Sites where function may become compromised, especially the eyelid, lip, nose, and finger.

▸ Sites where complete closure may cause ischemia or necrosis.

"You don't have to close every defect," said Dr. Hamill of the department of dermatology at the University of South Florida, Tampa, who also has a private dermatology practice in Hudson, Fla.

Many areas granulate well without any closure, especially in the concave areas on the nose, eyelid, ear, and temple—the so-called NEET areas (J. Am. Acad. Dermatol. 1983;9:407–15).

Surgical scars will have the best results when they are kept within anatomical units (especially the eyelids, nose, lips, and ears), and are best hidden within the lines of relaxed tension. Indeed, an overriding principle is that "the best surgical scar is the one you don't need to extend," he said.

Partial closures allow you to shorten a scar and to decrease overall surgery time, a particularly important consideration in elderly patients.

Some preliminary data even suggest that partial closures—by not creating a dead space—may be associated with a reduced risk of postsurgical infection. Avoiding infection is becoming especially critical in this era of methicillin-resistant Staphylococcus aureus, Dr. Hamill said.

It's important to warn patients that there will be a small hole or wound in the area you've partially closed, which may take up to 2–3 weeks to completely heal. During this time, there may be crusting or oozing that may require cleaning. Depending on their comfort level, patients can either clean the wound themselves or come back to your office.

"Patients are very receptive to partial closures as long as you tell them up front what to expect," said Dr. Hamill.

Partial closure is also the best option any time there is a risk for ectropion. "If a closure results in pulling, I always adjust the flap by placing the patient in a seated position and removing sutures, [thereby] creating a partial closure so there is no ectropion immediately after suturing," he noted.

In some cases, it may even make sense to consider a partial closure after a complete one in areas of high tension, such as the leg or scalp. If you've done a complete closure in such an area, try waiting 5 minutes, he advised.

If the area looks white and ischemic, you may want to take out a few sutures to create a partial closure. This will allow the flap to completely take and is always better than partial necrosis. A clinical pearl is to debride the new partial defect every 2 weeks so that the defect heals from within, thus preventing a depressed scar, he said.

And another clinical pearl: When using a simple transposition flap, it may be possible to subdivide the defect to create two separate but smaller areas of granulation, rather than one larger area. Doing so may reduce the healing time and produce a smaller scar. This technique is especially useful on the nose if a complete closure pulls the tip and results in congested breathing.

"You can make a very complex closure simple and prevent functional deficit," Dr. Hamill said.

Overall, the aim is to "keep it simple and work with nature," he said.

This patient had ectropion that resulted from the closure of a lateral advancement flap used to repair a defect on her lower eyelid.

The partial closure was created by removing the medial superior sutures until the ectropion was no longer present.

One month after surgery, there is no ectropion with only minimal swelling, which eventually resolved over the next few months. Photos courtesy Dr. J. Robert Hamill Jr.

LUCAYA, BAHAMAS — Partial closure is an underutilized technique that can improve the outcome of surgical reconstruction after Mohs surgery for many patients, Dr. J. Robert Hamill Jr. said at a meeting of the American Society for Mohs Surgery.

Indeed, closing only part of the wound and leaving the rest to granulate on its own is advantageous in a wide variety of situations. Surgical sites to consider for partial closure include:

▸ Tumor sites that need to be monitored for recurrence.

▸ Surgical sites under high tension, including the leg, scalp, and fingers.

▸ Sites where function may become compromised, especially the eyelid, lip, nose, and finger.

▸ Sites where complete closure may cause ischemia or necrosis.

"You don't have to close every defect," said Dr. Hamill of the department of dermatology at the University of South Florida, Tampa, who also has a private dermatology practice in Hudson, Fla.

Many areas granulate well without any closure, especially in the concave areas on the nose, eyelid, ear, and temple—the so-called NEET areas (J. Am. Acad. Dermatol. 1983;9:407–15).

Surgical scars will have the best results when they are kept within anatomical units (especially the eyelids, nose, lips, and ears), and are best hidden within the lines of relaxed tension. Indeed, an overriding principle is that "the best surgical scar is the one you don't need to extend," he said.

Partial closures allow you to shorten a scar and to decrease overall surgery time, a particularly important consideration in elderly patients.

Some preliminary data even suggest that partial closures—by not creating a dead space—may be associated with a reduced risk of postsurgical infection. Avoiding infection is becoming especially critical in this era of methicillin-resistant Staphylococcus aureus, Dr. Hamill said.

It's important to warn patients that there will be a small hole or wound in the area you've partially closed, which may take up to 2–3 weeks to completely heal. During this time, there may be crusting or oozing that may require cleaning. Depending on their comfort level, patients can either clean the wound themselves or come back to your office.

"Patients are very receptive to partial closures as long as you tell them up front what to expect," said Dr. Hamill.

Partial closure is also the best option any time there is a risk for ectropion. "If a closure results in pulling, I always adjust the flap by placing the patient in a seated position and removing sutures, [thereby] creating a partial closure so there is no ectropion immediately after suturing," he noted.

In some cases, it may even make sense to consider a partial closure after a complete one in areas of high tension, such as the leg or scalp. If you've done a complete closure in such an area, try waiting 5 minutes, he advised.

If the area looks white and ischemic, you may want to take out a few sutures to create a partial closure. This will allow the flap to completely take and is always better than partial necrosis. A clinical pearl is to debride the new partial defect every 2 weeks so that the defect heals from within, thus preventing a depressed scar, he said.

And another clinical pearl: When using a simple transposition flap, it may be possible to subdivide the defect to create two separate but smaller areas of granulation, rather than one larger area. Doing so may reduce the healing time and produce a smaller scar. This technique is especially useful on the nose if a complete closure pulls the tip and results in congested breathing.

"You can make a very complex closure simple and prevent functional deficit," Dr. Hamill said.

Overall, the aim is to "keep it simple and work with nature," he said.

This patient had ectropion that resulted from the closure of a lateral advancement flap used to repair a defect on her lower eyelid.

The partial closure was created by removing the medial superior sutures until the ectropion was no longer present.

One month after surgery, there is no ectropion with only minimal swelling, which eventually resolved over the next few months. Photos courtesy Dr. J. Robert Hamill Jr.

LUCAYA, BAHAMAS — Partial closure is an underutilized technique that can improve the outcome of surgical reconstruction after Mohs surgery for many patients, Dr. J. Robert Hamill Jr. said at a meeting of the American Society for Mohs Surgery.

Indeed, closing only part of the wound and leaving the rest to granulate on its own is advantageous in a wide variety of situations. Surgical sites to consider for partial closure include:

▸ Tumor sites that need to be monitored for recurrence.

▸ Surgical sites under high tension, including the leg, scalp, and fingers.

▸ Sites where function may become compromised, especially the eyelid, lip, nose, and finger.

▸ Sites where complete closure may cause ischemia or necrosis.

"You don't have to close every defect," said Dr. Hamill of the department of dermatology at the University of South Florida, Tampa, who also has a private dermatology practice in Hudson, Fla.

Many areas granulate well without any closure, especially in the concave areas on the nose, eyelid, ear, and temple—the so-called NEET areas (J. Am. Acad. Dermatol. 1983;9:407–15).

Surgical scars will have the best results when they are kept within anatomical units (especially the eyelids, nose, lips, and ears), and are best hidden within the lines of relaxed tension. Indeed, an overriding principle is that "the best surgical scar is the one you don't need to extend," he said.

Partial closures allow you to shorten a scar and to decrease overall surgery time, a particularly important consideration in elderly patients.

Some preliminary data even suggest that partial closures—by not creating a dead space—may be associated with a reduced risk of postsurgical infection. Avoiding infection is becoming especially critical in this era of methicillin-resistant Staphylococcus aureus, Dr. Hamill said.

It's important to warn patients that there will be a small hole or wound in the area you've partially closed, which may take up to 2–3 weeks to completely heal. During this time, there may be crusting or oozing that may require cleaning. Depending on their comfort level, patients can either clean the wound themselves or come back to your office.

"Patients are very receptive to partial closures as long as you tell them up front what to expect," said Dr. Hamill.

Partial closure is also the best option any time there is a risk for ectropion. "If a closure results in pulling, I always adjust the flap by placing the patient in a seated position and removing sutures, [thereby] creating a partial closure so there is no ectropion immediately after suturing," he noted.

In some cases, it may even make sense to consider a partial closure after a complete one in areas of high tension, such as the leg or scalp. If you've done a complete closure in such an area, try waiting 5 minutes, he advised.

If the area looks white and ischemic, you may want to take out a few sutures to create a partial closure. This will allow the flap to completely take and is always better than partial necrosis. A clinical pearl is to debride the new partial defect every 2 weeks so that the defect heals from within, thus preventing a depressed scar, he said.

And another clinical pearl: When using a simple transposition flap, it may be possible to subdivide the defect to create two separate but smaller areas of granulation, rather than one larger area. Doing so may reduce the healing time and produce a smaller scar. This technique is especially useful on the nose if a complete closure pulls the tip and results in congested breathing.

"You can make a very complex closure simple and prevent functional deficit," Dr. Hamill said.

Overall, the aim is to "keep it simple and work with nature," he said.

This patient had ectropion that resulted from the closure of a lateral advancement flap used to repair a defect on her lower eyelid.

The partial closure was created by removing the medial superior sutures until the ectropion was no longer present.

One month after surgery, there is no ectropion with only minimal swelling, which eventually resolved over the next few months. Photos courtesy Dr. J. Robert Hamill Jr.

PHILADELPHIA — Liver biopsy is losing its appeal as a diagnostic tool for chronic liver disease, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Problems associated with liver biopsy such as sampling error, inadequate specimens, and interobserver variability have become increasingly apparent in recent years, whereas noninvasive markers of fibrosis and inflammation are showing more promise as diagnostic tools.

Overall, liver biopsy is assuming a role more as a prognostic test than as a diagnostic test. At the very least, it should not be used “as a knee-jerk response to hepatic biochemical test abnormalities,” said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

Studies published in the past 3–8 years suggest that because liver biopsy samples less than 1/50,000 of the liver, cirrhosis may be missed in up to 20% of patients. Moreover, grades of inflammation and stage of fibrosis may be underscored in short, narrow specimens. Obtaining an adequate specimen—ideally more than 2.5 cm long, more than 1.4 mm wide, and with 11 or more portal triads—is often a challenge.

Panels of noninvasive markers of fibrosis and inflammation are not quite “ready for prime time,” but such tests may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. In addition, an ultrasonographic tool called FibroScan is being evaluated in Europe.

The relative pros and cons of doing a liver biopsy depend on the condition. With hepatitis C, biopsy may help determine the extent of fibrosis and inflammation, which are the best predictors of disease progression. On the other hand, noninvasive markers may also accurately stage and grade disease.

In hepatitis C patients with genotype 1, which carries the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with the more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy.

Biopsy can help determine the need for treatment in patients experiencing side effects or in those who were previously treated and therefore less likely to respond to retreatment. However, “we don't really have effective retreatment strategies,” he said.

With hepatitis B, the decision to treat is generally made with hepatitis B serologies, viral DNA, and ALT, although biopsy might be considered in patients with fluctuating ALT levels. And, although biopsy might prompt screening for varices and hepatocellular carcinoma (HCC) in a patient with hepatitis B, surveillance for HCC is recommended in these patients whether cirrhosis is present or not, he noted.

For patients with elevated ALT levels, a biopsy can help confirm a diagnosis. However, a cause for abnormal hepatic biochemical tests is accurately identified clinically in more than 90% of cases without a biopsy. Similarly, the diagnosis of nonalcoholic fatty liver disease (NAFLD) is also usually made clinically, although not all patients have classic risk factors. Currently, only biopsy can distinguish simple steatosis from steatohepatitis, although noninvasive markers may accomplish this in the future.

Although the presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, there is no proven therapy for NAFLD. The absence of steatohepatitis or fibrosis might remove that motivation, Dr. Reddy cautioned.

Overall, he said, “noninvasive markers may be as 'good' or as 'flawed' as a liver biopsy, and may complement a liver biopsy rather than replace it—time will tell.”

Noninvasive markers 'may complement a liver biopsy rather than replace it—time will tell.' DR. REDDY

PHILADELPHIA — Liver biopsy is losing its appeal as a diagnostic tool for chronic liver disease, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Problems associated with liver biopsy such as sampling error, inadequate specimens, and interobserver variability have become increasingly apparent in recent years, whereas noninvasive markers of fibrosis and inflammation are showing more promise as diagnostic tools.

Overall, liver biopsy is assuming a role more as a prognostic test than as a diagnostic test. At the very least, it should not be used “as a knee-jerk response to hepatic biochemical test abnormalities,” said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

Studies published in the past 3–8 years suggest that because liver biopsy samples less than 1/50,000 of the liver, cirrhosis may be missed in up to 20% of patients. Moreover, grades of inflammation and stage of fibrosis may be underscored in short, narrow specimens. Obtaining an adequate specimen—ideally more than 2.5 cm long, more than 1.4 mm wide, and with 11 or more portal triads—is often a challenge.

Panels of noninvasive markers of fibrosis and inflammation are not quite “ready for prime time,” but such tests may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. In addition, an ultrasonographic tool called FibroScan is being evaluated in Europe.

The relative pros and cons of doing a liver biopsy depend on the condition. With hepatitis C, biopsy may help determine the extent of fibrosis and inflammation, which are the best predictors of disease progression. On the other hand, noninvasive markers may also accurately stage and grade disease.

In hepatitis C patients with genotype 1, which carries the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with the more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy.

Biopsy can help determine the need for treatment in patients experiencing side effects or in those who were previously treated and therefore less likely to respond to retreatment. However, “we don't really have effective retreatment strategies,” he said.

With hepatitis B, the decision to treat is generally made with hepatitis B serologies, viral DNA, and ALT, although biopsy might be considered in patients with fluctuating ALT levels. And, although biopsy might prompt screening for varices and hepatocellular carcinoma (HCC) in a patient with hepatitis B, surveillance for HCC is recommended in these patients whether cirrhosis is present or not, he noted.

For patients with elevated ALT levels, a biopsy can help confirm a diagnosis. However, a cause for abnormal hepatic biochemical tests is accurately identified clinically in more than 90% of cases without a biopsy. Similarly, the diagnosis of nonalcoholic fatty liver disease (NAFLD) is also usually made clinically, although not all patients have classic risk factors. Currently, only biopsy can distinguish simple steatosis from steatohepatitis, although noninvasive markers may accomplish this in the future.

Although the presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, there is no proven therapy for NAFLD. The absence of steatohepatitis or fibrosis might remove that motivation, Dr. Reddy cautioned.

Overall, he said, “noninvasive markers may be as 'good' or as 'flawed' as a liver biopsy, and may complement a liver biopsy rather than replace it—time will tell.”

Noninvasive markers 'may complement a liver biopsy rather than replace it—time will tell.' DR. REDDY

PHILADELPHIA — Liver biopsy is losing its appeal as a diagnostic tool for chronic liver disease, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Problems associated with liver biopsy such as sampling error, inadequate specimens, and interobserver variability have become increasingly apparent in recent years, whereas noninvasive markers of fibrosis and inflammation are showing more promise as diagnostic tools.

Overall, liver biopsy is assuming a role more as a prognostic test than as a diagnostic test. At the very least, it should not be used “as a knee-jerk response to hepatic biochemical test abnormalities,” said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

Studies published in the past 3–8 years suggest that because liver biopsy samples less than 1/50,000 of the liver, cirrhosis may be missed in up to 20% of patients. Moreover, grades of inflammation and stage of fibrosis may be underscored in short, narrow specimens. Obtaining an adequate specimen—ideally more than 2.5 cm long, more than 1.4 mm wide, and with 11 or more portal triads—is often a challenge.

Panels of noninvasive markers of fibrosis and inflammation are not quite “ready for prime time,” but such tests may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. In addition, an ultrasonographic tool called FibroScan is being evaluated in Europe.

The relative pros and cons of doing a liver biopsy depend on the condition. With hepatitis C, biopsy may help determine the extent of fibrosis and inflammation, which are the best predictors of disease progression. On the other hand, noninvasive markers may also accurately stage and grade disease.

In hepatitis C patients with genotype 1, which carries the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with the more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy.

Biopsy can help determine the need for treatment in patients experiencing side effects or in those who were previously treated and therefore less likely to respond to retreatment. However, “we don't really have effective retreatment strategies,” he said.

With hepatitis B, the decision to treat is generally made with hepatitis B serologies, viral DNA, and ALT, although biopsy might be considered in patients with fluctuating ALT levels. And, although biopsy might prompt screening for varices and hepatocellular carcinoma (HCC) in a patient with hepatitis B, surveillance for HCC is recommended in these patients whether cirrhosis is present or not, he noted.

For patients with elevated ALT levels, a biopsy can help confirm a diagnosis. However, a cause for abnormal hepatic biochemical tests is accurately identified clinically in more than 90% of cases without a biopsy. Similarly, the diagnosis of nonalcoholic fatty liver disease (NAFLD) is also usually made clinically, although not all patients have classic risk factors. Currently, only biopsy can distinguish simple steatosis from steatohepatitis, although noninvasive markers may accomplish this in the future.

Although the presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, there is no proven therapy for NAFLD. The absence of steatohepatitis or fibrosis might remove that motivation, Dr. Reddy cautioned.

Overall, he said, “noninvasive markers may be as 'good' or as 'flawed' as a liver biopsy, and may complement a liver biopsy rather than replace it—time will tell.”

Noninvasive markers 'may complement a liver biopsy rather than replace it—time will tell.' DR. REDDY

PHILADELPHIA — An investigational bronchoscopic procedure marketed as Bronchial Thermoplasty may offer an effective, safe, and permanent treatment for the small proportion of patients with severe asthma who cannot be controlled with conventional medications, Dr. Alan R. Leff said at the annual meeting of the American College of Physicians.

About 10% of all asthma patients have severe disease that is inadequately responsive to available treatments with β-agonists, corticosteroids, or leukotriene modifiers. All of these therapies are directed at the active disease state, rather than modifying the underlying disease process.

Bronchial Thermoplasty, in contrast, aims to permanently “undo” the contractile ability of airway smooth muscle, thereby preventing bronchoconstriction, explained Dr. Leff, professor of medicine, pediatrics, anesthesiology, and critical care at the University of Chicago.

Dr. Leff is a consultant for Asthmatx Inc. (www.asthmatx.com

The treatment involves application of heat via the bronchoscope into all airways with diameters of 3 mm or more, and selectively ablating the airway smooth muscle—which is particularly heat sensitive—while preserving other tissues.

All experimental evidence points to the fact that this is safe because mammalian airway smooth muscle is vestigial and has no function. “In neither human nor animal studies has there been anything to indicate that airway smooth muscle really does anything … the goal of all asthma treatment is to get as little airway smooth muscle tone as possible. Clearly, asthma patients are better off the less tone they have.”

In a preliminary study, 16 patients with mild to moderate asthma underwent Bronchial Thermoplasty. The procedure was well tolerated, with side effects that were transient and typical of effects commonly observed after bronchoscopy.

Reductions in airway hyperresponsiveness occurred in all 16 patients, with a mean increase of 2.37 doublings of the PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) at 12 weeks. At 1 year post procedure, the mean increase in PC20 was 2.77 doublings, and at 2 years, it was 2.64 doublings, Dr. Gerard Cox and his associates reported (Am. J. Respir. Crit. Care Med. 2006;173:965–9).

Data from daily diaries collected for 12 weeks indicated significant improvements over baseline in symptom-free days, morning peak flow, and evening peak flow measurements, while spirometry measurements remained stable throughout the study period, said Dr. Cox and his associates from the institute for respiratory health at McMaster University, Hamilton, Ontario.

Preliminary trials of Bronchial Thermoplasty have been conducted in patients with only mild to moderate disease (forced expiratory volume in 1 second greater than 80% predicted) to ensure that the treatment would not exacerbate human asthma, which cannot be replicated in an animal model.

In follow-up data that have now reached a duration of 3 years, there has been continued improvement, with no worsening seen. “It's looking like the improvement is pretty much a permanent thing,” Dr. Leff noted. Several clinical studies are now underway in patients with moderate to severe asthma, the group for whom the treatment would be indicated.

Dr. Leff said the procedure is typically accomplished in two or three half-hour sessions, roughly the length of an average bronchoscopy.

In an editorial that accompanied the published article, Dr. Elisabeth H. Bel said the study “suggests that Bronchial Thermoplasty has the potential to become a realistic therapeutic option in chronic asthma not satisfactorily controlled with pharmacotherapy.”

However, Dr. Bel, doctor of medicine and philosophy in the pulmonology department at Leiden University Medical Center, the Netherlands, added two cautionary notes. For one, the long-term consequences of the procedure are unknown, and it is possible that problems such as permanent widening of the large airways, chronic infections, or increased airway wall collapsibility might appear over time. “Therefore, long-term observation of subjects undergoing this procedure is mandatory,” she said.

Secondly, it is not yet clear to what degree Bronchial Thermoplasty targets the peripheral airways and it may well be that inadequate treatment of those airways may be the primary reason that patients with refractory asthma do not respond satisfactorily to inhaled therapy. If patients refrain from pharmacotherapy because of symptom improvement following this procedure, the distal airways could become even more inflamed and obstructed than before. Long-term data from the ongoing studies involving patients with moderate to severe asthma will shed further light on the issue.

“Bronchial Thermoplasty should never be applied without proper anti-inflammatory pharmacotherapy in these patients,” said Dr. Bel. He has been a speaker at meetings financed by several pharmaceutical companies and was on the advisory board for Merck, Sharpe & Dohme Ltd. until 2005.

PHILADELPHIA — An investigational bronchoscopic procedure marketed as Bronchial Thermoplasty may offer an effective, safe, and permanent treatment for the small proportion of patients with severe asthma who cannot be controlled with conventional medications, Dr. Alan R. Leff said at the annual meeting of the American College of Physicians.

About 10% of all asthma patients have severe disease that is inadequately responsive to available treatments with β-agonists, corticosteroids, or leukotriene modifiers. All of these therapies are directed at the active disease state, rather than modifying the underlying disease process.

Bronchial Thermoplasty, in contrast, aims to permanently “undo” the contractile ability of airway smooth muscle, thereby preventing bronchoconstriction, explained Dr. Leff, professor of medicine, pediatrics, anesthesiology, and critical care at the University of Chicago.

Dr. Leff is a consultant for Asthmatx Inc. (www.asthmatx.com

The treatment involves application of heat via the bronchoscope into all airways with diameters of 3 mm or more, and selectively ablating the airway smooth muscle—which is particularly heat sensitive—while preserving other tissues.

All experimental evidence points to the fact that this is safe because mammalian airway smooth muscle is vestigial and has no function. “In neither human nor animal studies has there been anything to indicate that airway smooth muscle really does anything … the goal of all asthma treatment is to get as little airway smooth muscle tone as possible. Clearly, asthma patients are better off the less tone they have.”

In a preliminary study, 16 patients with mild to moderate asthma underwent Bronchial Thermoplasty. The procedure was well tolerated, with side effects that were transient and typical of effects commonly observed after bronchoscopy.

Reductions in airway hyperresponsiveness occurred in all 16 patients, with a mean increase of 2.37 doublings of the PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) at 12 weeks. At 1 year post procedure, the mean increase in PC20 was 2.77 doublings, and at 2 years, it was 2.64 doublings, Dr. Gerard Cox and his associates reported (Am. J. Respir. Crit. Care Med. 2006;173:965–9).

Data from daily diaries collected for 12 weeks indicated significant improvements over baseline in symptom-free days, morning peak flow, and evening peak flow measurements, while spirometry measurements remained stable throughout the study period, said Dr. Cox and his associates from the institute for respiratory health at McMaster University, Hamilton, Ontario.

Preliminary trials of Bronchial Thermoplasty have been conducted in patients with only mild to moderate disease (forced expiratory volume in 1 second greater than 80% predicted) to ensure that the treatment would not exacerbate human asthma, which cannot be replicated in an animal model.

In follow-up data that have now reached a duration of 3 years, there has been continued improvement, with no worsening seen. “It's looking like the improvement is pretty much a permanent thing,” Dr. Leff noted. Several clinical studies are now underway in patients with moderate to severe asthma, the group for whom the treatment would be indicated.

Dr. Leff said the procedure is typically accomplished in two or three half-hour sessions, roughly the length of an average bronchoscopy.

In an editorial that accompanied the published article, Dr. Elisabeth H. Bel said the study “suggests that Bronchial Thermoplasty has the potential to become a realistic therapeutic option in chronic asthma not satisfactorily controlled with pharmacotherapy.”

However, Dr. Bel, doctor of medicine and philosophy in the pulmonology department at Leiden University Medical Center, the Netherlands, added two cautionary notes. For one, the long-term consequences of the procedure are unknown, and it is possible that problems such as permanent widening of the large airways, chronic infections, or increased airway wall collapsibility might appear over time. “Therefore, long-term observation of subjects undergoing this procedure is mandatory,” she said.

Secondly, it is not yet clear to what degree Bronchial Thermoplasty targets the peripheral airways and it may well be that inadequate treatment of those airways may be the primary reason that patients with refractory asthma do not respond satisfactorily to inhaled therapy. If patients refrain from pharmacotherapy because of symptom improvement following this procedure, the distal airways could become even more inflamed and obstructed than before. Long-term data from the ongoing studies involving patients with moderate to severe asthma will shed further light on the issue.

“Bronchial Thermoplasty should never be applied without proper anti-inflammatory pharmacotherapy in these patients,” said Dr. Bel. He has been a speaker at meetings financed by several pharmaceutical companies and was on the advisory board for Merck, Sharpe & Dohme Ltd. until 2005.

PHILADELPHIA — An investigational bronchoscopic procedure marketed as Bronchial Thermoplasty may offer an effective, safe, and permanent treatment for the small proportion of patients with severe asthma who cannot be controlled with conventional medications, Dr. Alan R. Leff said at the annual meeting of the American College of Physicians.

About 10% of all asthma patients have severe disease that is inadequately responsive to available treatments with β-agonists, corticosteroids, or leukotriene modifiers. All of these therapies are directed at the active disease state, rather than modifying the underlying disease process.

Bronchial Thermoplasty, in contrast, aims to permanently “undo” the contractile ability of airway smooth muscle, thereby preventing bronchoconstriction, explained Dr. Leff, professor of medicine, pediatrics, anesthesiology, and critical care at the University of Chicago.

Dr. Leff is a consultant for Asthmatx Inc. (www.asthmatx.com

The treatment involves application of heat via the bronchoscope into all airways with diameters of 3 mm or more, and selectively ablating the airway smooth muscle—which is particularly heat sensitive—while preserving other tissues.

All experimental evidence points to the fact that this is safe because mammalian airway smooth muscle is vestigial and has no function. “In neither human nor animal studies has there been anything to indicate that airway smooth muscle really does anything … the goal of all asthma treatment is to get as little airway smooth muscle tone as possible. Clearly, asthma patients are better off the less tone they have.”

In a preliminary study, 16 patients with mild to moderate asthma underwent Bronchial Thermoplasty. The procedure was well tolerated, with side effects that were transient and typical of effects commonly observed after bronchoscopy.

Reductions in airway hyperresponsiveness occurred in all 16 patients, with a mean increase of 2.37 doublings of the PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) at 12 weeks. At 1 year post procedure, the mean increase in PC20 was 2.77 doublings, and at 2 years, it was 2.64 doublings, Dr. Gerard Cox and his associates reported (Am. J. Respir. Crit. Care Med. 2006;173:965–9).

Data from daily diaries collected for 12 weeks indicated significant improvements over baseline in symptom-free days, morning peak flow, and evening peak flow measurements, while spirometry measurements remained stable throughout the study period, said Dr. Cox and his associates from the institute for respiratory health at McMaster University, Hamilton, Ontario.

Preliminary trials of Bronchial Thermoplasty have been conducted in patients with only mild to moderate disease (forced expiratory volume in 1 second greater than 80% predicted) to ensure that the treatment would not exacerbate human asthma, which cannot be replicated in an animal model.

In follow-up data that have now reached a duration of 3 years, there has been continued improvement, with no worsening seen. “It's looking like the improvement is pretty much a permanent thing,” Dr. Leff noted. Several clinical studies are now underway in patients with moderate to severe asthma, the group for whom the treatment would be indicated.

Dr. Leff said the procedure is typically accomplished in two or three half-hour sessions, roughly the length of an average bronchoscopy.

In an editorial that accompanied the published article, Dr. Elisabeth H. Bel said the study “suggests that Bronchial Thermoplasty has the potential to become a realistic therapeutic option in chronic asthma not satisfactorily controlled with pharmacotherapy.”

However, Dr. Bel, doctor of medicine and philosophy in the pulmonology department at Leiden University Medical Center, the Netherlands, added two cautionary notes. For one, the long-term consequences of the procedure are unknown, and it is possible that problems such as permanent widening of the large airways, chronic infections, or increased airway wall collapsibility might appear over time. “Therefore, long-term observation of subjects undergoing this procedure is mandatory,” she said.

Secondly, it is not yet clear to what degree Bronchial Thermoplasty targets the peripheral airways and it may well be that inadequate treatment of those airways may be the primary reason that patients with refractory asthma do not respond satisfactorily to inhaled therapy. If patients refrain from pharmacotherapy because of symptom improvement following this procedure, the distal airways could become even more inflamed and obstructed than before. Long-term data from the ongoing studies involving patients with moderate to severe asthma will shed further light on the issue.

“Bronchial Thermoplasty should never be applied without proper anti-inflammatory pharmacotherapy in these patients,” said Dr. Bel. He has been a speaker at meetings financed by several pharmaceutical companies and was on the advisory board for Merck, Sharpe & Dohme Ltd. until 2005.