Miriam E. Tucker

AMELIA ISLAND, FLA. — Every case of melanonychia striata must be evaluated individually, Dr. Richard K. Scher said at a symposium sponsored by the Dermatology Foundation.

Longitudinal bands of pigmentation in nails are among the trickiest of dermatologic phenomena to diagnose. Unlike the approach to cutaneous lesions that may or may not be melanoma, there are no reliable clinical or histologic criteria to help the clinician determine the melanoma probability of any given pigmented nail band. Some general prognostic information is available, but exceptions come along far too often for a physician to feel secure in a diagnosis.

“You can't trust the nail. It just doesn't follow the rules you try to use when evaluating skin lesions,” said Dr. Scher, professor of clinical dermatology at Columbia University, New York.

Melanonychia striata affect about 1% of whites and 11% of Japanese individuals. One study found that among blacks, the prevalence rises dramatically with age, from 2.5% of children aged 0–3 years to 77% of adults older than 20 years, to 96% of those older than 50 years. But the risk is very pigment dependent, with darker-skinned blacks having higher rates than those with lighter complexions.

Melanonychia and subungual melanoma are most common in the thumb, great toe, and index finger, so it's particularly important to examine all the finger and toe nails of patients who have pigmented bands in any of those three areas. But, keep in mind that 20% of subungual melanoma are amelanotic, Dr. Scher warned.

Clinical features of the pigmentation can provide clues, but not reliable answers. In general, the lighter and more narrow the band, the less likely it is to be melanoma. However, “I've seen 1- to 2-mm pigmented bands which were melanoma in situ, light bands that were melanoma, and dark bands that were not melanoma.” And of course, a fungal infection also can present as a dark black nail band.

Hyperpigmentation that extends into the proximal nail fold, known as “Hutchinson's sign,” is melanoma until proved otherwise. Sometimes it is something other than melanoma, in which case it's called “pseudo-Hutchinson's sign.”

Uniformity of color is a good sign, whereas bands that are darker in some areas than others are more likely to be melanoma. Pigmentation that covers the entire nail also increases the melanoma probability. And, as with cutaneous lesions, a nail band that changes in color or size over time requires urgent evaluation. Involvement of multiple digits makes melanoma less likely, but any one that looks distinctly different from the others “should be regarded with some degree of suspicion,” Dr. Scher said.

Because the nail matrix is the source of pigmentation (about 90% of melanocytic bands arise from the distal matrix and 10% from the proximal matrix) biopsies must be taken from the nail matrix and not the nail bed. A recent article has described the use of dermoscopy of the free edge of the nail to determine the level of nail plate pigmentation and the location of its probable origin in the proximal or distal matrix (J. Am. Acad. Dermatol. 2006;55:512–3). But, there are no standardized criteria for the use of dermoscopy in melanonychia, and the procedure requires training and expertise, but “dermoscopy can help distinguish [subungual hematoma] from melanoma.”

The role of trauma in subungual melan- oma is controversial. Some people believe it is a contributing factor, others say evidence does not support that idea. About 25% of subungual melanomas have a history of trauma to the nail. This can prove to be a diagnostic nightmare, given that even the confirmed presence of a subungual hematoma does not exclude the possibility of a coexisting cancerous lesion.

The probability of melanonychia striata in children is far lower than it is in adults, comprising just 1%–4% of all melanomas in individuals less than 20 years of age. The new thinking is that, because most melanonychia striata in children are nevi and not melanoma, observation during childhood is an option as long as the lesions are stable and not atypical in appearance. In general it's still a good idea to biopsy any lesion you're uncomfortable with. “When in doubt, biopsy,” Dr. Scher said.

From left to right: malignant melanoma that arose from longitudinal melanonychia; longitudinal melanonychia that proved to be melanoma in situ; biopsy from melanoma in situ

From left to right: longitudinal melanonychia caused by a benign melanotic macule/lentigo; another case resulting from a fungal melanonychia; and another resulting from a nevus. Photos courtesy Dr. Richard K. Scher

AMELIA ISLAND, FLA. — Every case of melanonychia striata must be evaluated individually, Dr. Richard K. Scher said at a symposium sponsored by the Dermatology Foundation.

Longitudinal bands of pigmentation in nails are among the trickiest of dermatologic phenomena to diagnose. Unlike the approach to cutaneous lesions that may or may not be melanoma, there are no reliable clinical or histologic criteria to help the clinician determine the melanoma probability of any given pigmented nail band. Some general prognostic information is available, but exceptions come along far too often for a physician to feel secure in a diagnosis.

“You can't trust the nail. It just doesn't follow the rules you try to use when evaluating skin lesions,” said Dr. Scher, professor of clinical dermatology at Columbia University, New York.

Melanonychia striata affect about 1% of whites and 11% of Japanese individuals. One study found that among blacks, the prevalence rises dramatically with age, from 2.5% of children aged 0–3 years to 77% of adults older than 20 years, to 96% of those older than 50 years. But the risk is very pigment dependent, with darker-skinned blacks having higher rates than those with lighter complexions.

Melanonychia and subungual melanoma are most common in the thumb, great toe, and index finger, so it's particularly important to examine all the finger and toe nails of patients who have pigmented bands in any of those three areas. But, keep in mind that 20% of subungual melanoma are amelanotic, Dr. Scher warned.

Clinical features of the pigmentation can provide clues, but not reliable answers. In general, the lighter and more narrow the band, the less likely it is to be melanoma. However, “I've seen 1- to 2-mm pigmented bands which were melanoma in situ, light bands that were melanoma, and dark bands that were not melanoma.” And of course, a fungal infection also can present as a dark black nail band.

Hyperpigmentation that extends into the proximal nail fold, known as “Hutchinson's sign,” is melanoma until proved otherwise. Sometimes it is something other than melanoma, in which case it's called “pseudo-Hutchinson's sign.”

Uniformity of color is a good sign, whereas bands that are darker in some areas than others are more likely to be melanoma. Pigmentation that covers the entire nail also increases the melanoma probability. And, as with cutaneous lesions, a nail band that changes in color or size over time requires urgent evaluation. Involvement of multiple digits makes melanoma less likely, but any one that looks distinctly different from the others “should be regarded with some degree of suspicion,” Dr. Scher said.

Because the nail matrix is the source of pigmentation (about 90% of melanocytic bands arise from the distal matrix and 10% from the proximal matrix) biopsies must be taken from the nail matrix and not the nail bed. A recent article has described the use of dermoscopy of the free edge of the nail to determine the level of nail plate pigmentation and the location of its probable origin in the proximal or distal matrix (J. Am. Acad. Dermatol. 2006;55:512–3). But, there are no standardized criteria for the use of dermoscopy in melanonychia, and the procedure requires training and expertise, but “dermoscopy can help distinguish [subungual hematoma] from melanoma.”

The role of trauma in subungual melan- oma is controversial. Some people believe it is a contributing factor, others say evidence does not support that idea. About 25% of subungual melanomas have a history of trauma to the nail. This can prove to be a diagnostic nightmare, given that even the confirmed presence of a subungual hematoma does not exclude the possibility of a coexisting cancerous lesion.

The probability of melanonychia striata in children is far lower than it is in adults, comprising just 1%–4% of all melanomas in individuals less than 20 years of age. The new thinking is that, because most melanonychia striata in children are nevi and not melanoma, observation during childhood is an option as long as the lesions are stable and not atypical in appearance. In general it's still a good idea to biopsy any lesion you're uncomfortable with. “When in doubt, biopsy,” Dr. Scher said.

From left to right: malignant melanoma that arose from longitudinal melanonychia; longitudinal melanonychia that proved to be melanoma in situ; biopsy from melanoma in situ

From left to right: longitudinal melanonychia caused by a benign melanotic macule/lentigo; another case resulting from a fungal melanonychia; and another resulting from a nevus. Photos courtesy Dr. Richard K. Scher

AMELIA ISLAND, FLA. — Every case of melanonychia striata must be evaluated individually, Dr. Richard K. Scher said at a symposium sponsored by the Dermatology Foundation.

Longitudinal bands of pigmentation in nails are among the trickiest of dermatologic phenomena to diagnose. Unlike the approach to cutaneous lesions that may or may not be melanoma, there are no reliable clinical or histologic criteria to help the clinician determine the melanoma probability of any given pigmented nail band. Some general prognostic information is available, but exceptions come along far too often for a physician to feel secure in a diagnosis.

“You can't trust the nail. It just doesn't follow the rules you try to use when evaluating skin lesions,” said Dr. Scher, professor of clinical dermatology at Columbia University, New York.

Melanonychia striata affect about 1% of whites and 11% of Japanese individuals. One study found that among blacks, the prevalence rises dramatically with age, from 2.5% of children aged 0–3 years to 77% of adults older than 20 years, to 96% of those older than 50 years. But the risk is very pigment dependent, with darker-skinned blacks having higher rates than those with lighter complexions.

Melanonychia and subungual melanoma are most common in the thumb, great toe, and index finger, so it's particularly important to examine all the finger and toe nails of patients who have pigmented bands in any of those three areas. But, keep in mind that 20% of subungual melanoma are amelanotic, Dr. Scher warned.

Clinical features of the pigmentation can provide clues, but not reliable answers. In general, the lighter and more narrow the band, the less likely it is to be melanoma. However, “I've seen 1- to 2-mm pigmented bands which were melanoma in situ, light bands that were melanoma, and dark bands that were not melanoma.” And of course, a fungal infection also can present as a dark black nail band.

Hyperpigmentation that extends into the proximal nail fold, known as “Hutchinson's sign,” is melanoma until proved otherwise. Sometimes it is something other than melanoma, in which case it's called “pseudo-Hutchinson's sign.”

Uniformity of color is a good sign, whereas bands that are darker in some areas than others are more likely to be melanoma. Pigmentation that covers the entire nail also increases the melanoma probability. And, as with cutaneous lesions, a nail band that changes in color or size over time requires urgent evaluation. Involvement of multiple digits makes melanoma less likely, but any one that looks distinctly different from the others “should be regarded with some degree of suspicion,” Dr. Scher said.

Because the nail matrix is the source of pigmentation (about 90% of melanocytic bands arise from the distal matrix and 10% from the proximal matrix) biopsies must be taken from the nail matrix and not the nail bed. A recent article has described the use of dermoscopy of the free edge of the nail to determine the level of nail plate pigmentation and the location of its probable origin in the proximal or distal matrix (J. Am. Acad. Dermatol. 2006;55:512–3). But, there are no standardized criteria for the use of dermoscopy in melanonychia, and the procedure requires training and expertise, but “dermoscopy can help distinguish [subungual hematoma] from melanoma.”

The role of trauma in subungual melan- oma is controversial. Some people believe it is a contributing factor, others say evidence does not support that idea. About 25% of subungual melanomas have a history of trauma to the nail. This can prove to be a diagnostic nightmare, given that even the confirmed presence of a subungual hematoma does not exclude the possibility of a coexisting cancerous lesion.

The probability of melanonychia striata in children is far lower than it is in adults, comprising just 1%–4% of all melanomas in individuals less than 20 years of age. The new thinking is that, because most melanonychia striata in children are nevi and not melanoma, observation during childhood is an option as long as the lesions are stable and not atypical in appearance. In general it's still a good idea to biopsy any lesion you're uncomfortable with. “When in doubt, biopsy,” Dr. Scher said.

From left to right: malignant melanoma that arose from longitudinal melanonychia; longitudinal melanonychia that proved to be melanoma in situ; biopsy from melanoma in situ

From left to right: longitudinal melanonychia caused by a benign melanotic macule/lentigo; another case resulting from a fungal melanonychia; and another resulting from a nevus. Photos courtesy Dr. Richard K. Scher

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine.

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older.

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck & Co., West Point, Pa.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups, by 2.6 in the younger group, compared with 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60% reporting one or more total adverse events, compared with 44% of the 60-plus group. Vaccine-related adverse events were reported by 52% and 35%, respectively. Injection-site reactions were the most common of these, reported by 50% of the younger subjects and 34% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 6% and 3%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine.

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older.

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck & Co., West Point, Pa.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups, by 2.6 in the younger group, compared with 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60% reporting one or more total adverse events, compared with 44% of the 60-plus group. Vaccine-related adverse events were reported by 52% and 35%, respectively. Injection-site reactions were the most common of these, reported by 50% of the younger subjects and 34% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 6% and 3%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine.

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older.

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck & Co., West Point, Pa.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups, by 2.6 in the younger group, compared with 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60% reporting one or more total adverse events, compared with 44% of the 60-plus group. Vaccine-related adverse events were reported by 52% and 35%, respectively. Injection-site reactions were the most common of these, reported by 50% of the younger subjects and 34% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 6% and 3%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

Medtronic's real-time continuous glucose monitoring devices will be available for use in children aged 7–17 years later this year.

The company's REAL-Time Continuous Glucose Monitor (CGM) systems, previously approved by the Food and Drug Administration only for adults, will be available in specifically designed pediatric models of both the stand-alone Guardian Real-Time CGM system and the Paradigm REAL-Time system, which combines an insulin pump with a continuous glucose monitor in a single unit.

The REAL-Time systems display glucose values every 5 minutes, along with trend graphs and directional arrows. They also issue alarms when glucose levels rise too high or drop too low. The pediatric alarm threshold is set at a minimum of 90 mg/dL, while the adult CGM low-glucose threshold is set at 50 mg/dL. Patients can adjust those thresholds higher, but not lower. In both adult and pediatric versions, the high-alert threshold default is 280 mg/dL, which can be adjusted up or down.

Dr. Daniel Einhorn, secretary of the American Association of Clinical Endocrinologists, was enthusiastic about the availability of these devices for children. “This is very exciting technology, and it's most exciting when it comes to kids,” he said. “For one thing, they can have some of the most erratic blood glucose swings. They are not the easiest group to get to do frequent blood glucose monitoring. … For parents, it's very reassuring to have alarms for high and low blood sugar.”

Pivotal data for FDA approval of Medtronic's current CGM technology came from a 12-week international study of 162 patients with type 1 diabetes, including 81 children aged 8–18.9 years (median 14.4 years) and 81 adults aged 19–59.5 years (median 39.1 years). At baseline, all subjects had hemoglobin A_1c levels of 8.1% or greater despite adhering to intensive insulin therapy with either a pump (78 patients) or multiple daily injections (84 patients).

Patients were randomly assigned for 3 months to one of three groups: CGM either always or for a 3-day period every other week, or conventional self-blood glucose monitoring (SBGM) via fingerstick, performed 4–5 times a day. Treatment adjustments based on the respective readings were made by physicians and patients. Patients were instructed to perform confirmatory SBGM measurements prior to either therapeutic interventions or corrective actions if the high or low alarm sounded, or if they had symptoms (Diabetes Care 2006;29:2730–2).

A total of 156 patients completed the evaluation. Hemoglobin A_1c values at 1 month dropped in the continuous CGM group by 0.6 percentage points from a baseline mean of 9.5%, compared with just 0.2 from a baseline mean of 9.7% in the SBGM-only (control) group. At 3 months, the reductions were 1.0% vs. 0.4%. Reductions in HbA_1c in the group using CGM intermittently did not differ significantly from either of the other groups.

At 3 months, 50% of the patients using CGM continuously had HbA_1c reductions of 1 percentage point or greater, compared with 37% in the intermittent CGM group and 15% of the controls. One-fourth of the continuous CGM group had reductions of 2 percentage points or greater, compared with 9% and 4%, respectively.

Total insulin doses did not differ significantly among the three groups at 3 months. Severe hypoglycemia occurred once each in two CGM patients, but one of them, from the intermittent use group, was not wearing the device at the time.

Currently, the information obtained from CGM devices is meant to illustrate patterns, not to make therapeutic decisions. Patients still need to perform SBGM fingersticks for that, as well as for twice-daily calibration of the machines.

Dr. Einhorn, who is medical director of the Scripps Whittier Institute for Diabetes, in San Diego, acknowledged that the current CGM devices still have some shortcomings that need to be worked out, including the fact that patients sometimes feel overwhelmed by the amount of data the devices generate.

However, he added, the American Association of Clinical Endocrinologists is enthusiastic about the technology and is urging insurance companies and Medicare to begin reimbursing for continuous glucose monitors. “This technology, even though first generation, is definitely ready for prime time.”

Medtronic's real-time continuous glucose monitoring devices will be available for use in children aged 7–17 years later this year.

The company's REAL-Time Continuous Glucose Monitor (CGM) systems, previously approved by the Food and Drug Administration only for adults, will be available in specifically designed pediatric models of both the stand-alone Guardian Real-Time CGM system and the Paradigm REAL-Time system, which combines an insulin pump with a continuous glucose monitor in a single unit.

The REAL-Time systems display glucose values every 5 minutes, along with trend graphs and directional arrows. They also issue alarms when glucose levels rise too high or drop too low. The pediatric alarm threshold is set at a minimum of 90 mg/dL, while the adult CGM low-glucose threshold is set at 50 mg/dL. Patients can adjust those thresholds higher, but not lower. In both adult and pediatric versions, the high-alert threshold default is 280 mg/dL, which can be adjusted up or down.

Dr. Daniel Einhorn, secretary of the American Association of Clinical Endocrinologists, was enthusiastic about the availability of these devices for children. “This is very exciting technology, and it's most exciting when it comes to kids,” he said. “For one thing, they can have some of the most erratic blood glucose swings. They are not the easiest group to get to do frequent blood glucose monitoring. … For parents, it's very reassuring to have alarms for high and low blood sugar.”

Pivotal data for FDA approval of Medtronic's current CGM technology came from a 12-week international study of 162 patients with type 1 diabetes, including 81 children aged 8–18.9 years (median 14.4 years) and 81 adults aged 19–59.5 years (median 39.1 years). At baseline, all subjects had hemoglobin A_1c levels of 8.1% or greater despite adhering to intensive insulin therapy with either a pump (78 patients) or multiple daily injections (84 patients).

Patients were randomly assigned for 3 months to one of three groups: CGM either always or for a 3-day period every other week, or conventional self-blood glucose monitoring (SBGM) via fingerstick, performed 4–5 times a day. Treatment adjustments based on the respective readings were made by physicians and patients. Patients were instructed to perform confirmatory SBGM measurements prior to either therapeutic interventions or corrective actions if the high or low alarm sounded, or if they had symptoms (Diabetes Care 2006;29:2730–2).

A total of 156 patients completed the evaluation. Hemoglobin A_1c values at 1 month dropped in the continuous CGM group by 0.6 percentage points from a baseline mean of 9.5%, compared with just 0.2 from a baseline mean of 9.7% in the SBGM-only (control) group. At 3 months, the reductions were 1.0% vs. 0.4%. Reductions in HbA_1c in the group using CGM intermittently did not differ significantly from either of the other groups.

At 3 months, 50% of the patients using CGM continuously had HbA_1c reductions of 1 percentage point or greater, compared with 37% in the intermittent CGM group and 15% of the controls. One-fourth of the continuous CGM group had reductions of 2 percentage points or greater, compared with 9% and 4%, respectively.

Total insulin doses did not differ significantly among the three groups at 3 months. Severe hypoglycemia occurred once each in two CGM patients, but one of them, from the intermittent use group, was not wearing the device at the time.

Currently, the information obtained from CGM devices is meant to illustrate patterns, not to make therapeutic decisions. Patients still need to perform SBGM fingersticks for that, as well as for twice-daily calibration of the machines.

Dr. Einhorn, who is medical director of the Scripps Whittier Institute for Diabetes, in San Diego, acknowledged that the current CGM devices still have some shortcomings that need to be worked out, including the fact that patients sometimes feel overwhelmed by the amount of data the devices generate.

However, he added, the American Association of Clinical Endocrinologists is enthusiastic about the technology and is urging insurance companies and Medicare to begin reimbursing for continuous glucose monitors. “This technology, even though first generation, is definitely ready for prime time.”

Medtronic's real-time continuous glucose monitoring devices will be available for use in children aged 7–17 years later this year.

The company's REAL-Time Continuous Glucose Monitor (CGM) systems, previously approved by the Food and Drug Administration only for adults, will be available in specifically designed pediatric models of both the stand-alone Guardian Real-Time CGM system and the Paradigm REAL-Time system, which combines an insulin pump with a continuous glucose monitor in a single unit.

The REAL-Time systems display glucose values every 5 minutes, along with trend graphs and directional arrows. They also issue alarms when glucose levels rise too high or drop too low. The pediatric alarm threshold is set at a minimum of 90 mg/dL, while the adult CGM low-glucose threshold is set at 50 mg/dL. Patients can adjust those thresholds higher, but not lower. In both adult and pediatric versions, the high-alert threshold default is 280 mg/dL, which can be adjusted up or down.

Dr. Daniel Einhorn, secretary of the American Association of Clinical Endocrinologists, was enthusiastic about the availability of these devices for children. “This is very exciting technology, and it's most exciting when it comes to kids,” he said. “For one thing, they can have some of the most erratic blood glucose swings. They are not the easiest group to get to do frequent blood glucose monitoring. … For parents, it's very reassuring to have alarms for high and low blood sugar.”

Pivotal data for FDA approval of Medtronic's current CGM technology came from a 12-week international study of 162 patients with type 1 diabetes, including 81 children aged 8–18.9 years (median 14.4 years) and 81 adults aged 19–59.5 years (median 39.1 years). At baseline, all subjects had hemoglobin A_1c levels of 8.1% or greater despite adhering to intensive insulin therapy with either a pump (78 patients) or multiple daily injections (84 patients).

Patients were randomly assigned for 3 months to one of three groups: CGM either always or for a 3-day period every other week, or conventional self-blood glucose monitoring (SBGM) via fingerstick, performed 4–5 times a day. Treatment adjustments based on the respective readings were made by physicians and patients. Patients were instructed to perform confirmatory SBGM measurements prior to either therapeutic interventions or corrective actions if the high or low alarm sounded, or if they had symptoms (Diabetes Care 2006;29:2730–2).

A total of 156 patients completed the evaluation. Hemoglobin A_1c values at 1 month dropped in the continuous CGM group by 0.6 percentage points from a baseline mean of 9.5%, compared with just 0.2 from a baseline mean of 9.7% in the SBGM-only (control) group. At 3 months, the reductions were 1.0% vs. 0.4%. Reductions in HbA_1c in the group using CGM intermittently did not differ significantly from either of the other groups.

At 3 months, 50% of the patients using CGM continuously had HbA_1c reductions of 1 percentage point or greater, compared with 37% in the intermittent CGM group and 15% of the controls. One-fourth of the continuous CGM group had reductions of 2 percentage points or greater, compared with 9% and 4%, respectively.

Total insulin doses did not differ significantly among the three groups at 3 months. Severe hypoglycemia occurred once each in two CGM patients, but one of them, from the intermittent use group, was not wearing the device at the time.

Currently, the information obtained from CGM devices is meant to illustrate patterns, not to make therapeutic decisions. Patients still need to perform SBGM fingersticks for that, as well as for twice-daily calibration of the machines.

Dr. Einhorn, who is medical director of the Scripps Whittier Institute for Diabetes, in San Diego, acknowledged that the current CGM devices still have some shortcomings that need to be worked out, including the fact that patients sometimes feel overwhelmed by the amount of data the devices generate.

However, he added, the American Association of Clinical Endocrinologists is enthusiastic about the technology and is urging insurance companies and Medicare to begin reimbursing for continuous glucose monitors. “This technology, even though first generation, is definitely ready for prime time.”

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine (INTERNAL MEDICINE NEWS, Jan. 15, 2006, p. 1).

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older (INTERNAL MEDICINE NEWS, Nov. 15, 2006, p. 1).

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups: by 2.6 in the younger group and 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60.3% reporting one or more, compared with 44.2% of the 60-plus group. Vaccine-related adverse events were reported by 51.9% and 35.1%, respectively. Injection-site reactions were the most common, reported by 50.4% of the younger subjects and 34.1% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 5.7% and 2.9%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

In response to a question from the audience as to the reason that local reactions are more common in 50- to 59-year-olds than in older adults, Dr. Jeffrey L. Silber, Merck's senior director of Vaccine/Infectious Disease Clinical Research, responded that the same phenomenon has been observed in the company's studies of other vaccines, even among placebo recipients. The data show that “people aged 50–59 simply complain more,” he said. “They also tend to have more headaches, perhaps because they're working and have more teenagers at home.”

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

The SPS also showed that the vaccine was generally well tolerated and that varicella zoster virus antibody response measured at 6 weeks post vaccination correlated with protection against herpes zoster, Dr. Sutradhar noted.

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine (INTERNAL MEDICINE NEWS, Jan. 15, 2006, p. 1).

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older (INTERNAL MEDICINE NEWS, Nov. 15, 2006, p. 1).

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups: by 2.6 in the younger group and 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60.3% reporting one or more, compared with 44.2% of the 60-plus group. Vaccine-related adverse events were reported by 51.9% and 35.1%, respectively. Injection-site reactions were the most common, reported by 50.4% of the younger subjects and 34.1% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 5.7% and 2.9%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

In response to a question from the audience as to the reason that local reactions are more common in 50- to 59-year-olds than in older adults, Dr. Jeffrey L. Silber, Merck's senior director of Vaccine/Infectious Disease Clinical Research, responded that the same phenomenon has been observed in the company's studies of other vaccines, even among placebo recipients. The data show that “people aged 50–59 simply complain more,” he said. “They also tend to have more headaches, perhaps because they're working and have more teenagers at home.”

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

The SPS also showed that the vaccine was generally well tolerated and that varicella zoster virus antibody response measured at 6 weeks post vaccination correlated with protection against herpes zoster, Dr. Sutradhar noted.

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

BALTIMORE — The herpes zoster vaccine is as immunogenic in adults aged 50–59 as it is in those aged 60 and older, Santosh C. Sutradhar, Ph.D., reported at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Zostavax, manufactured by Merck & Co., was licensed by the U.S. Food and Drug Administration in May 2006 for the prevention of herpes zoster in adults aged 60 and older only. Merck had sought an indication for those aged 50–59 years, but an earlier FDA advisory panel had recommended against it because data on safety and efficacy in that age group were lacking, as were overall data on duration of immunity for the vaccine (INTERNAL MEDICINE NEWS, Jan. 15, 2006, p. 1).

In October 2006, the Advisory Committee on Immunization Practices recommended universal use of Zostavax among adults aged 60 and older (INTERNAL MEDICINE NEWS, Nov. 15, 2006, p. 1).

Nonetheless, epidemiologic data suggest that the annual risk of developing herpes zoster actually begins to increase markedly around age 50 years and rises sharply afterward. Thus, “it is important to assess the immunogenicity and safety of Zostavax in this age group,” said Dr. Sutradhar, senior biometrician at Merck.

In combined data from two protocols that had been presented separately to the FDA, the vaccine was administered to 389 subjects aged 50–59 and to 733 aged 60 and older. Of those, 377 and 731, respectively, completed the 28-day follow-up. Antibody response, assessed by geometric mean fold rise of varicella zoster virus antibody from prevaccination to 4 weeks post vaccination, was increased substantially in both groups: by 2.6 in the younger group and 2.3 in the older subjects.

Both of those levels exceeded the predefined threshold for “acceptable” antibody response, and the response for the younger group met the “noninferiority” criteria, compared with that of the older group, he said.

Adverse events within 28 days following vaccination were more common in the 50- to 59-year-olds, with 60.3% reporting one or more, compared with 44.2% of the 60-plus group. Vaccine-related adverse events were reported by 51.9% and 35.1%, respectively. Injection-site reactions were the most common, reported by 50.4% of the younger subjects and 34.1% of the older ones. Systemic vaccine-related adverse events were far less common, reported by 5.7% and 2.9%, respectively, and no subject in either age group reported any serious vaccine-related adverse events.

In response to a question from the audience as to the reason that local reactions are more common in 50- to 59-year-olds than in older adults, Dr. Jeffrey L. Silber, Merck's senior director of Vaccine/Infectious Disease Clinical Research, responded that the same phenomenon has been observed in the company's studies of other vaccines, even among placebo recipients. The data show that “people aged 50–59 simply complain more,” he said. “They also tend to have more headaches, perhaps because they're working and have more teenagers at home.”

Merck is working with the FDA to develop a protocol that will provide vaccine efficacy data as well as additional safety data specifically for the 50- to 59-year-old age group, as had been done previously with those aged 60 and older in the Shingles Prevention Study (SPS). Those findings, from more than 38,000 adults older than 60, showed that the vaccine reduced the burden of illness related to herpes zoster pain, the incidence of postherpetic neuralgia, and the incidence of herpes zoster (N. Engl. J. Med. 2005;352:2271–84).

The SPS also showed that the vaccine was generally well tolerated and that varicella zoster virus antibody response measured at 6 weeks post vaccination correlated with protection against herpes zoster, Dr. Sutradhar noted.

Merck hopes to launch the new protocol sometime this year, according to a company spokeswoman.

Be alert for severe cases of community-acquired pneumonia that might be caused by methicillin-resistant Staphylococcus aureus, the Centers for Disease Control and Prevention advised.

Although uncommon, community-acquired pneumonia (CAP) can be caused by methicillin-resistant S. aureus (MRSA). Such cases often affect young, otherwise healthy individuals and can be rapidly fatal. MRSA should be suspected in patients with severe pneumonia, especially during the influenza season, and in those with cavitary infiltrates. The index of suspicion for MRSA CAP should be particularly increased in those who have a history of MRSA skin infection or who have had close contact with MRSA-infected individuals, the CDC said (MMWR 2007;56:325–9).

During December 2006 to January 2007, 10 cases of severe MRSA CAP were reported to the CDC from Louisiana and Georgia. Patient ages ranged from 4 months to 48 years; eight were younger than 30 years. Five were female and five male. Six of the 10 patients died, including 4 children aged 8–14 years.

One patient had a history of chronic hepatitis C and hypertension, and two were current smokers. Four had documentation of recent MRSA skin and soft-tissue infection or were living with someone who did. In all 10 cases, influenzalike illness had been diagnosed prior to or concurrent with CAP. Six patients had laboratory-confirmed influenza. Of six for whom vaccination status was available, none had received influenza vaccine for the 2006–2007 season. Radiologic information, available for all 10 patients, showed unilobar infiltrates in 3 and multilobar infiltrates in 7. In three patients, MRSA was isolated from sputum only.

Particularly notable was the short period between any respiratory symptom onset and either death or recovery of MRSA from the patient: Respiratory symptoms began a median of 3 days (range 2–6 days) before collection of specimens that grew MRSA. Of the six patients who died, the median period from onset to death was 3.5 days (range 2–25 days); four of the six died within 4 days of symptom onset.

These short durations suggest that the influenza virus and the MRSA infections probably occurred concomitantly, the CDC noted.

Be alert for severe cases of community-acquired pneumonia that might be caused by methicillin-resistant Staphylococcus aureus, the Centers for Disease Control and Prevention advised.

Although uncommon, community-acquired pneumonia (CAP) can be caused by methicillin-resistant S. aureus (MRSA). Such cases often affect young, otherwise healthy individuals and can be rapidly fatal. MRSA should be suspected in patients with severe pneumonia, especially during the influenza season, and in those with cavitary infiltrates. The index of suspicion for MRSA CAP should be particularly increased in those who have a history of MRSA skin infection or who have had close contact with MRSA-infected individuals, the CDC said (MMWR 2007;56:325–9).

During December 2006 to January 2007, 10 cases of severe MRSA CAP were reported to the CDC from Louisiana and Georgia. Patient ages ranged from 4 months to 48 years; eight were younger than 30 years. Five were female and five male. Six of the 10 patients died, including 4 children aged 8–14 years.

One patient had a history of chronic hepatitis C and hypertension, and two were current smokers. Four had documentation of recent MRSA skin and soft-tissue infection or were living with someone who did. In all 10 cases, influenzalike illness had been diagnosed prior to or concurrent with CAP. Six patients had laboratory-confirmed influenza. Of six for whom vaccination status was available, none had received influenza vaccine for the 2006–2007 season. Radiologic information, available for all 10 patients, showed unilobar infiltrates in 3 and multilobar infiltrates in 7. In three patients, MRSA was isolated from sputum only.

Particularly notable was the short period between any respiratory symptom onset and either death or recovery of MRSA from the patient: Respiratory symptoms began a median of 3 days (range 2–6 days) before collection of specimens that grew MRSA. Of the six patients who died, the median period from onset to death was 3.5 days (range 2–25 days); four of the six died within 4 days of symptom onset.

These short durations suggest that the influenza virus and the MRSA infections probably occurred concomitantly, the CDC noted.

Be alert for severe cases of community-acquired pneumonia that might be caused by methicillin-resistant Staphylococcus aureus, the Centers for Disease Control and Prevention advised.

Although uncommon, community-acquired pneumonia (CAP) can be caused by methicillin-resistant S. aureus (MRSA). Such cases often affect young, otherwise healthy individuals and can be rapidly fatal. MRSA should be suspected in patients with severe pneumonia, especially during the influenza season, and in those with cavitary infiltrates. The index of suspicion for MRSA CAP should be particularly increased in those who have a history of MRSA skin infection or who have had close contact with MRSA-infected individuals, the CDC said (MMWR 2007;56:325–9).

During December 2006 to January 2007, 10 cases of severe MRSA CAP were reported to the CDC from Louisiana and Georgia. Patient ages ranged from 4 months to 48 years; eight were younger than 30 years. Five were female and five male. Six of the 10 patients died, including 4 children aged 8–14 years.

One patient had a history of chronic hepatitis C and hypertension, and two were current smokers. Four had documentation of recent MRSA skin and soft-tissue infection or were living with someone who did. In all 10 cases, influenzalike illness had been diagnosed prior to or concurrent with CAP. Six patients had laboratory-confirmed influenza. Of six for whom vaccination status was available, none had received influenza vaccine for the 2006–2007 season. Radiologic information, available for all 10 patients, showed unilobar infiltrates in 3 and multilobar infiltrates in 7. In three patients, MRSA was isolated from sputum only.

Particularly notable was the short period between any respiratory symptom onset and either death or recovery of MRSA from the patient: Respiratory symptoms began a median of 3 days (range 2–6 days) before collection of specimens that grew MRSA. Of the six patients who died, the median period from onset to death was 3.5 days (range 2–25 days); four of the six died within 4 days of symptom onset.

These short durations suggest that the influenza virus and the MRSA infections probably occurred concomitantly, the CDC noted.

The cost of diabetes complications in the United States topped $22 billion in 2006, according to a new report released at the annual meeting of the American Association of Clinical Endocrinologists.

The report, titled State of Diabetes Complications in America, is part of an educational campaign sponsored by AACE in collaboration with a “diabetes complications consortium” comprising the Amputee Coalition of America, Mended Hearts (a nationwide patient support group affiliated with the American Heart Association), the National Federation of the Blind, and the National Kidney Foundation. The project is funded by GlaxoSmithKline.

“There is a rather linear progression between how poorly controlled the diabetes is and how long it's poorly controlled, and whether you [develop] complications. So, the earlier you intervene and the more aggressively you intervene, the lower your risk for developing complications. We have known this for some time. What's remarkable about this report is that despite knowing this and despite having the tools to control blood glucose, we are still getting this high burden of complications,” Dr. Daniel Einhorn, secretary of AACE's board of directors, said at a press briefing held during the AACE annual meeting.

Data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) suggest dramatic differences in both macrovascular and microvascular disease between people with diagnosed type 2 diabetes and those without (see box). Heart attack, for example, occurs in 9.8% of diabetic patients, compared with 1.8% of those with normal blood glucose levels; coronary heart disease in 9.1% vs. 2.1%; and stroke in 6.6% vs. 1.8%.

As expected, microvascular complications affect people with diabetes even more disproportionately: 27.8% vs. 6.1% for chronic kidney disease and 22.9% vs. 10% for foot problems (including amputations, foot lesions, and numbness). Retinopathy was assessed among only NHANES participants who reported a diagnosis of diabetes, with the question “Have you been told diabetes has affected your eyes/had retinopathy?” The proportion responding affirmatively was 18.9%.

Overall, 58% of those with diagnosed diabetes reported having one or more microvascular and/or macrovascular complications. Approximately 33% reported one complication, 10% had two, and nearly 7% had three.

Annual direct health care costs were assessed from the 2000, 2002, and 2004 Medical Expenditure Panel Survey. The total per capita cost of diabetes plus its complications (adjusted for inflation to reflect 2006 dollar amounts) was $9,797, of which $1,566 was out of pocket. In contrast, the total cost for people with diabetes but experiencing the same rate of complications as those without diabetes totaled $8,039, while the cost for people without diabetes (and with average complication rates) was $2,848.

Total annual direct expenditures were $22.9 billion for diabetes complications alone and $57.1 billion for diabetes plus its complications. Out-of-pocket costs were $1.8 billion and $8.4 billion, respectively. Those amounts don't include costs attributed to lost employment or productivity, premature death, or disability.

Among the complications, the most expensive per patient was heart attack, at $14,150, followed by chronic kidney disease ($9,002), congestive heart failure ($7,932), and stroke ($7,806). Among the microvascular complications, the total per-patient expenditure for foot problems was $4,687 and for eye damage (including retinopathy, cataracts, glaucoma, and blindness), $1,785.

The diabetes complications consortium was formed “to provide helpful information to people with type 2 diabetes about how to reduce the risk of the health complications associated with the disease, as well as support and encouragement to people who have experienced these serious health problems.” The group's Web site is www.stateofdiabetes.com

ELSEVIER GLOBAL MEDICAL NEWS

The cost of diabetes complications in the United States topped $22 billion in 2006, according to a new report released at the annual meeting of the American Association of Clinical Endocrinologists.

The report, titled State of Diabetes Complications in America, is part of an educational campaign sponsored by AACE in collaboration with a “diabetes complications consortium” comprising the Amputee Coalition of America, Mended Hearts (a nationwide patient support group affiliated with the American Heart Association), the National Federation of the Blind, and the National Kidney Foundation. The project is funded by GlaxoSmithKline.

“There is a rather linear progression between how poorly controlled the diabetes is and how long it's poorly controlled, and whether you [develop] complications. So, the earlier you intervene and the more aggressively you intervene, the lower your risk for developing complications. We have known this for some time. What's remarkable about this report is that despite knowing this and despite having the tools to control blood glucose, we are still getting this high burden of complications,” Dr. Daniel Einhorn, secretary of AACE's board of directors, said at a press briefing held during the AACE annual meeting.

Data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) suggest dramatic differences in both macrovascular and microvascular disease between people with diagnosed type 2 diabetes and those without (see box). Heart attack, for example, occurs in 9.8% of diabetic patients, compared with 1.8% of those with normal blood glucose levels; coronary heart disease in 9.1% vs. 2.1%; and stroke in 6.6% vs. 1.8%.

As expected, microvascular complications affect people with diabetes even more disproportionately: 27.8% vs. 6.1% for chronic kidney disease and 22.9% vs. 10% for foot problems (including amputations, foot lesions, and numbness). Retinopathy was assessed among only NHANES participants who reported a diagnosis of diabetes, with the question “Have you been told diabetes has affected your eyes/had retinopathy?” The proportion responding affirmatively was 18.9%.

Overall, 58% of those with diagnosed diabetes reported having one or more microvascular and/or macrovascular complications. Approximately 33% reported one complication, 10% had two, and nearly 7% had three.

Annual direct health care costs were assessed from the 2000, 2002, and 2004 Medical Expenditure Panel Survey. The total per capita cost of diabetes plus its complications (adjusted for inflation to reflect 2006 dollar amounts) was $9,797, of which $1,566 was out of pocket. In contrast, the total cost for people with diabetes but experiencing the same rate of complications as those without diabetes totaled $8,039, while the cost for people without diabetes (and with average complication rates) was $2,848.

Total annual direct expenditures were $22.9 billion for diabetes complications alone and $57.1 billion for diabetes plus its complications. Out-of-pocket costs were $1.8 billion and $8.4 billion, respectively. Those amounts don't include costs attributed to lost employment or productivity, premature death, or disability.

Among the complications, the most expensive per patient was heart attack, at $14,150, followed by chronic kidney disease ($9,002), congestive heart failure ($7,932), and stroke ($7,806). Among the microvascular complications, the total per-patient expenditure for foot problems was $4,687 and for eye damage (including retinopathy, cataracts, glaucoma, and blindness), $1,785.

The diabetes complications consortium was formed “to provide helpful information to people with type 2 diabetes about how to reduce the risk of the health complications associated with the disease, as well as support and encouragement to people who have experienced these serious health problems.” The group's Web site is www.stateofdiabetes.com

ELSEVIER GLOBAL MEDICAL NEWS

The cost of diabetes complications in the United States topped $22 billion in 2006, according to a new report released at the annual meeting of the American Association of Clinical Endocrinologists.

The report, titled State of Diabetes Complications in America, is part of an educational campaign sponsored by AACE in collaboration with a “diabetes complications consortium” comprising the Amputee Coalition of America, Mended Hearts (a nationwide patient support group affiliated with the American Heart Association), the National Federation of the Blind, and the National Kidney Foundation. The project is funded by GlaxoSmithKline.

“There is a rather linear progression between how poorly controlled the diabetes is and how long it's poorly controlled, and whether you [develop] complications. So, the earlier you intervene and the more aggressively you intervene, the lower your risk for developing complications. We have known this for some time. What's remarkable about this report is that despite knowing this and despite having the tools to control blood glucose, we are still getting this high burden of complications,” Dr. Daniel Einhorn, secretary of AACE's board of directors, said at a press briefing held during the AACE annual meeting.

Data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) suggest dramatic differences in both macrovascular and microvascular disease between people with diagnosed type 2 diabetes and those without (see box). Heart attack, for example, occurs in 9.8% of diabetic patients, compared with 1.8% of those with normal blood glucose levels; coronary heart disease in 9.1% vs. 2.1%; and stroke in 6.6% vs. 1.8%.

As expected, microvascular complications affect people with diabetes even more disproportionately: 27.8% vs. 6.1% for chronic kidney disease and 22.9% vs. 10% for foot problems (including amputations, foot lesions, and numbness). Retinopathy was assessed among only NHANES participants who reported a diagnosis of diabetes, with the question “Have you been told diabetes has affected your eyes/had retinopathy?” The proportion responding affirmatively was 18.9%.

Overall, 58% of those with diagnosed diabetes reported having one or more microvascular and/or macrovascular complications. Approximately 33% reported one complication, 10% had two, and nearly 7% had three.

Annual direct health care costs were assessed from the 2000, 2002, and 2004 Medical Expenditure Panel Survey. The total per capita cost of diabetes plus its complications (adjusted for inflation to reflect 2006 dollar amounts) was $9,797, of which $1,566 was out of pocket. In contrast, the total cost for people with diabetes but experiencing the same rate of complications as those without diabetes totaled $8,039, while the cost for people without diabetes (and with average complication rates) was $2,848.

Total annual direct expenditures were $22.9 billion for diabetes complications alone and $57.1 billion for diabetes plus its complications. Out-of-pocket costs were $1.8 billion and $8.4 billion, respectively. Those amounts don't include costs attributed to lost employment or productivity, premature death, or disability.

Among the complications, the most expensive per patient was heart attack, at $14,150, followed by chronic kidney disease ($9,002), congestive heart failure ($7,932), and stroke ($7,806). Among the microvascular complications, the total per-patient expenditure for foot problems was $4,687 and for eye damage (including retinopathy, cataracts, glaucoma, and blindness), $1,785.

The diabetes complications consortium was formed “to provide helpful information to people with type 2 diabetes about how to reduce the risk of the health complications associated with the disease, as well as support and encouragement to people who have experienced these serious health problems.” The group's Web site is www.stateofdiabetes.com

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Intralesional bleomycin should continue to be a therapeutic option for treating plantar warts, Dr. William Stebbins said in a poster presentation at the annual meeting of the American Academy of Dermatology.

The efficacy of the antineoplastic agent bleomycin against recalcitrant plantar warts comes from its ability to bind to human papillomavirus DNA, resulting in single-strand breaks, direct cytotoxic effects, virucidal effects, and upregulation of tumor necrosis factor-α (J. Exp. Med. 1989;170:655–63).

Bleomycin is associated with injection pain and rare systemic events, so it is less commonly used for wart treatment than are other methods such as cryosurgery, laser treatment, or immunotherapy. But intralesional bleomycin can be effective in patients with especially large plantar warts that are resistant to other therapies, or for patients who want resolution of their warts in weeks rather than months.

In one of the few studies of intralesional bleomycin to include patient satisfaction as an outcome measure, Dr. Stebbins, a first-year dermatology resident at Mount Sinai Hospital, New York, and his associates reviewed 33 patients with one or more plantar or periungual warts who had received their last bleomycin injection at least 12 months prior to the study. Data were gathered from chart reviews and telephone interviews. The patients were 18 men and 15 women with a mean age of 39 years and a total of 257 treated warts.

Two-thirds of the patients had multiple warts, and most had attempted one or more other treatments unsuccessfully before undergoing the bleomycin injection. However, five of the patients, with 40 warts, were treatment naive, he noted.

Before the administration of bleomycin, the surgical site was anesthetized with lidocaine plus epinephrine using a 30-gauge needle. The wart was then pared down using a No. 15 scalpel blade. Bleomycin sulfate 3 U/cc was injected into the warty focus at a depth of 1–1.5 mm, using no more than 0.025–0.05 mL/3 mm2.

Treatment sessions were typically limited to a total dose of less than 3 U (or 1 mL) of bleomycin per area treated. Lower doses were delivered to the tips of the fingers or toes; slightly higher doses were used for large plantar lesions. The maximum total dose of bleomycin used in any one session was restricted to 5 U. Treated sites were covered with soft gauze, and a hemorrhagic callous was removed 2.5–3 weeks later.

This method resulted in complete resolution of all warts in 27 of the 33 patients: 16 of them after just one session and 22 after two sessions. All five treatment-naive patients experienced complete resolution, said Dr. Stebbins, who has no financial relationship with Bristol-Myers Squibb, manufacturer of bleomycin. Three-fourths of the patients reported a pain duration of less than 2 days, with one-third saying that their pain lasted less than 6 hours following the treatment, but five patients reported pain lasting more than 5 days. The average pain rating—including during and after the procedure—was 5.2 out of 10.

Other side effects included skin discoloration in one patient; callous formation in two patients; and pain, erythema, ulceration, and infection in one patient. There were no systemic or vascular side effects. In all, 26 of the 27 cured patients were satisfied with their treatment. One said it was too painful.

WASHINGTON — Intralesional bleomycin should continue to be a therapeutic option for treating plantar warts, Dr. William Stebbins said in a poster presentation at the annual meeting of the American Academy of Dermatology.

The efficacy of the antineoplastic agent bleomycin against recalcitrant plantar warts comes from its ability to bind to human papillomavirus DNA, resulting in single-strand breaks, direct cytotoxic effects, virucidal effects, and upregulation of tumor necrosis factor-α (J. Exp. Med. 1989;170:655–63).

Bleomycin is associated with injection pain and rare systemic events, so it is less commonly used for wart treatment than are other methods such as cryosurgery, laser treatment, or immunotherapy. But intralesional bleomycin can be effective in patients with especially large plantar warts that are resistant to other therapies, or for patients who want resolution of their warts in weeks rather than months.

In one of the few studies of intralesional bleomycin to include patient satisfaction as an outcome measure, Dr. Stebbins, a first-year dermatology resident at Mount Sinai Hospital, New York, and his associates reviewed 33 patients with one or more plantar or periungual warts who had received their last bleomycin injection at least 12 months prior to the study. Data were gathered from chart reviews and telephone interviews. The patients were 18 men and 15 women with a mean age of 39 years and a total of 257 treated warts.

Two-thirds of the patients had multiple warts, and most had attempted one or more other treatments unsuccessfully before undergoing the bleomycin injection. However, five of the patients, with 40 warts, were treatment naive, he noted.

Before the administration of bleomycin, the surgical site was anesthetized with lidocaine plus epinephrine using a 30-gauge needle. The wart was then pared down using a No. 15 scalpel blade. Bleomycin sulfate 3 U/cc was injected into the warty focus at a depth of 1–1.5 mm, using no more than 0.025–0.05 mL/3 mm2.

Treatment sessions were typically limited to a total dose of less than 3 U (or 1 mL) of bleomycin per area treated. Lower doses were delivered to the tips of the fingers or toes; slightly higher doses were used for large plantar lesions. The maximum total dose of bleomycin used in any one session was restricted to 5 U. Treated sites were covered with soft gauze, and a hemorrhagic callous was removed 2.5–3 weeks later.

This method resulted in complete resolution of all warts in 27 of the 33 patients: 16 of them after just one session and 22 after two sessions. All five treatment-naive patients experienced complete resolution, said Dr. Stebbins, who has no financial relationship with Bristol-Myers Squibb, manufacturer of bleomycin. Three-fourths of the patients reported a pain duration of less than 2 days, with one-third saying that their pain lasted less than 6 hours following the treatment, but five patients reported pain lasting more than 5 days. The average pain rating—including during and after the procedure—was 5.2 out of 10.

Other side effects included skin discoloration in one patient; callous formation in two patients; and pain, erythema, ulceration, and infection in one patient. There were no systemic or vascular side effects. In all, 26 of the 27 cured patients were satisfied with their treatment. One said it was too painful.

WASHINGTON — Intralesional bleomycin should continue to be a therapeutic option for treating plantar warts, Dr. William Stebbins said in a poster presentation at the annual meeting of the American Academy of Dermatology.

The efficacy of the antineoplastic agent bleomycin against recalcitrant plantar warts comes from its ability to bind to human papillomavirus DNA, resulting in single-strand breaks, direct cytotoxic effects, virucidal effects, and upregulation of tumor necrosis factor-α (J. Exp. Med. 1989;170:655–63).

Bleomycin is associated with injection pain and rare systemic events, so it is less commonly used for wart treatment than are other methods such as cryosurgery, laser treatment, or immunotherapy. But intralesional bleomycin can be effective in patients with especially large plantar warts that are resistant to other therapies, or for patients who want resolution of their warts in weeks rather than months.

In one of the few studies of intralesional bleomycin to include patient satisfaction as an outcome measure, Dr. Stebbins, a first-year dermatology resident at Mount Sinai Hospital, New York, and his associates reviewed 33 patients with one or more plantar or periungual warts who had received their last bleomycin injection at least 12 months prior to the study. Data were gathered from chart reviews and telephone interviews. The patients were 18 men and 15 women with a mean age of 39 years and a total of 257 treated warts.

Two-thirds of the patients had multiple warts, and most had attempted one or more other treatments unsuccessfully before undergoing the bleomycin injection. However, five of the patients, with 40 warts, were treatment naive, he noted.

Before the administration of bleomycin, the surgical site was anesthetized with lidocaine plus epinephrine using a 30-gauge needle. The wart was then pared down using a No. 15 scalpel blade. Bleomycin sulfate 3 U/cc was injected into the warty focus at a depth of 1–1.5 mm, using no more than 0.025–0.05 mL/3 mm2.

Treatment sessions were typically limited to a total dose of less than 3 U (or 1 mL) of bleomycin per area treated. Lower doses were delivered to the tips of the fingers or toes; slightly higher doses were used for large plantar lesions. The maximum total dose of bleomycin used in any one session was restricted to 5 U. Treated sites were covered with soft gauze, and a hemorrhagic callous was removed 2.5–3 weeks later.

This method resulted in complete resolution of all warts in 27 of the 33 patients: 16 of them after just one session and 22 after two sessions. All five treatment-naive patients experienced complete resolution, said Dr. Stebbins, who has no financial relationship with Bristol-Myers Squibb, manufacturer of bleomycin. Three-fourths of the patients reported a pain duration of less than 2 days, with one-third saying that their pain lasted less than 6 hours following the treatment, but five patients reported pain lasting more than 5 days. The average pain rating—including during and after the procedure—was 5.2 out of 10.

Other side effects included skin discoloration in one patient; callous formation in two patients; and pain, erythema, ulceration, and infection in one patient. There were no systemic or vascular side effects. In all, 26 of the 27 cured patients were satisfied with their treatment. One said it was too painful.

Fluoroquinolones should no longer be used for the treatment of gonorrhea in the United States, the Centers for Disease Control and Prevention has concluded.

The recommendation is based on new evidence suggesting that the prevalence of fluoroquinolone-resistant strains in the United States has now surpassed the prespecified threshold of 5%. Only one antimicrobial class—the cephalosporins—is now still recommended and available for the treatment of gonococcal infections or for other conditions that might be caused by Neisseria gonorrhoeae, such as pelvic inflammatory disease, the CDC said (MMWR 2007;56:332–6).

Fluoroquinolones have been used to treat gonorrhea since 1993. Between 1990 and 2001, the CDC's Gonococcal Isolate Surveillance Project (GISP) detected fluoroquinolone-resistant N. gonorrhoeae (QRNG) prevalences of less than 1% among urethral gonococcal isolates taken from males attending between 26 and 30 sexually transmitted disease clinics around the country.

But the prevalence rose to 2.2% in 2002, then to 4.1% in 2003, and to 6.8% in 2004. In 2005, 9.4% of 6,199 isolates collected by GISP were resistant to ciprofloxacin, and during January-June of 2006, 13.3% of 3,005 isolates were resistant.

“Gonorrhea has proven to be quite efficient at navigating around the drugs we use to combat it, developing resistance first to penicillin and tetracycline, and most recently to fluoroquinolones,” said Dr. John M. Douglas, director of the CDC's division of sexually transmitted diseases prevention, in a telebriefing held in conjunction with the release of the new guidelines.

Recommendations to stop the use of fluoroquinolones to treat gonorrhea had already been issued in 2000 for people who acquired their infections in Hawaii, and in 2002, the recommendation was extended to California.

In 2004, the CDC advised that fluoroquinolones should no longer be used to treat gonorrhea in men who have sex with men (MSM) throughout the United States. Excluding isolates from Hawaii and California, 6.1% of U.S. isolates in 2005 and 8.6% in 2006 were fluoroquinolone resistant, the CDC reported.

Data from GIST suggest that QRNG has been increasing among both MSM and heterosexual males since 2001. The prevalence among MSM, which was 1.6% in 2001, rose to 7.2% in 2002, 15% in 2003, 24% in 2004, and 29% in 2005. The increase has been slower among heterosexual males, from 0.9% in 2002 to 1.5% in 2003, 2.9% in 2004, and 3.8% in 2005.

Preliminary data from the first half of 2006 indicate that the QRNG prevalence was 38.3% among MSM and 6.7% among heterosexual males, with both numbers surpassing the 5% threshold set by both the CDC and the World Health Organization to ensure that all recommended gonorrhea treatments can be expected to cure 95% or more of infections, the CDC said.

Cephalosporins are now the only agents available in the United States that meet that standard. For the treatment of uncomplicated urogenital and anorectal gonorrhea, the CDC now recommends a single 125-mg intramuscular dose of ceftriaxone. A single oral 400-mg dose of cefixime is also recommended, but cefixime is available only in a suspension in the United States, not as 400-mg tablets.

Single oral doses of 400 mg cefpodoxime or 1 g cefuroxime axetil also are likely to be effective, but the data for those two regimens are more limited than for ceftriaxone, Dr. Douglas said during the briefing.

Alternative parenteral single-dose regimens for urogenital and anorectal gonorrhea include 500 mg ceftizoxime, 2 g cefoxitin with 1 g oral probenecid, or 500 mg cefotaxime.

However, these regimens don't offer any advantages over ceftriaxone, the CDC noted.

A single 125-mg dose of ceftriaxone also is the recommended treatment for uncomplicated gonococcal infections of the pharynx.

Updated regimens for disseminated gonococcal infection, pelvic inflammatory disease, epididymitis, and gonococcal infections in patients with documented severe allergic reactions to penicillins or cephalosporins are available in separate documents at www.cdc.gov/std/treatment

Unless Chlamydia trachomatis has been specifically ruled out, all patients diagnosed with gonococcal disease should also be treated for possible coinfection, with a single dose of 1 g azithromycin by mouth or with 100 mg doxycycline twice a day by mouth for 7 days.

The full gonorrhea treatment guidelines are available at www.cdc.gov/?std/gonorrhea/arg

Test of cure is not routinely recommended, but patients with persistent or recurring symptoms following treatment should be reevaluated by culture for N. gonorrhoeae, and any positive isolates should undergo antimicrobial susceptibility testing.

Treatment failures or resistant gonococcal isolates should be reported to the CDC at 404-639-8373 through state and local public health authorities.

Specifics of the New Guidelines For Gonorrhea

Because of increased fluoroquinolone resistance of Neisseria gonorrhoeae in the United States, the Centers for Disease Control and Prevention no longer recommends the use of that class of antimicrobials for treatment of gonococcal infections in adolescent or adult patients, regardless of travel or sexual behavior.

The CDC's new guidelines include these recommendations:

▸ Uncomplicated gonococcal infections of the cervix, urethra, and rectum. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, or cefixime 400 mg in a single oral dose, plus treatment for chlamydia if chlamydial infection is not ruled out. Alternative regimens: Spectinomycin (not available in the United States) 2 g in a single dose IM or cephalosporin single-dose regimens (including ceftizoxime 500 mg IM, or cefoxitin 2 g IM administered with probenecid 1 g orally, or cefotaxime 500 mg IM).

▸ Uncomplicated gonococcal infections of the pharynx. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, plus treatment for chlamydia if chlamydial infection is not ruled out.

Fluoroquinolones should no longer be used for the treatment of gonorrhea in the United States, the Centers for Disease Control and Prevention has concluded.

The recommendation is based on new evidence suggesting that the prevalence of fluoroquinolone-resistant strains in the United States has now surpassed the prespecified threshold of 5%. Only one antimicrobial class—the cephalosporins—is now still recommended and available for the treatment of gonococcal infections or for other conditions that might be caused by Neisseria gonorrhoeae, such as pelvic inflammatory disease, the CDC said (MMWR 2007;56:332–6).

Fluoroquinolones have been used to treat gonorrhea since 1993. Between 1990 and 2001, the CDC's Gonococcal Isolate Surveillance Project (GISP) detected fluoroquinolone-resistant N. gonorrhoeae (QRNG) prevalences of less than 1% among urethral gonococcal isolates taken from males attending between 26 and 30 sexually transmitted disease clinics around the country.

But the prevalence rose to 2.2% in 2002, then to 4.1% in 2003, and to 6.8% in 2004. In 2005, 9.4% of 6,199 isolates collected by GISP were resistant to ciprofloxacin, and during January-June of 2006, 13.3% of 3,005 isolates were resistant.

“Gonorrhea has proven to be quite efficient at navigating around the drugs we use to combat it, developing resistance first to penicillin and tetracycline, and most recently to fluoroquinolones,” said Dr. John M. Douglas, director of the CDC's division of sexually transmitted diseases prevention, in a telebriefing held in conjunction with the release of the new guidelines.

Recommendations to stop the use of fluoroquinolones to treat gonorrhea had already been issued in 2000 for people who acquired their infections in Hawaii, and in 2002, the recommendation was extended to California.

In 2004, the CDC advised that fluoroquinolones should no longer be used to treat gonorrhea in men who have sex with men (MSM) throughout the United States. Excluding isolates from Hawaii and California, 6.1% of U.S. isolates in 2005 and 8.6% in 2006 were fluoroquinolone resistant, the CDC reported.

Data from GIST suggest that QRNG has been increasing among both MSM and heterosexual males since 2001. The prevalence among MSM, which was 1.6% in 2001, rose to 7.2% in 2002, 15% in 2003, 24% in 2004, and 29% in 2005. The increase has been slower among heterosexual males, from 0.9% in 2002 to 1.5% in 2003, 2.9% in 2004, and 3.8% in 2005.

Preliminary data from the first half of 2006 indicate that the QRNG prevalence was 38.3% among MSM and 6.7% among heterosexual males, with both numbers surpassing the 5% threshold set by both the CDC and the World Health Organization to ensure that all recommended gonorrhea treatments can be expected to cure 95% or more of infections, the CDC said.

Cephalosporins are now the only agents available in the United States that meet that standard. For the treatment of uncomplicated urogenital and anorectal gonorrhea, the CDC now recommends a single 125-mg intramuscular dose of ceftriaxone. A single oral 400-mg dose of cefixime is also recommended, but cefixime is available only in a suspension in the United States, not as 400-mg tablets.

Single oral doses of 400 mg cefpodoxime or 1 g cefuroxime axetil also are likely to be effective, but the data for those two regimens are more limited than for ceftriaxone, Dr. Douglas said during the briefing.

Alternative parenteral single-dose regimens for urogenital and anorectal gonorrhea include 500 mg ceftizoxime, 2 g cefoxitin with 1 g oral probenecid, or 500 mg cefotaxime.

However, these regimens don't offer any advantages over ceftriaxone, the CDC noted.

A single 125-mg dose of ceftriaxone also is the recommended treatment for uncomplicated gonococcal infections of the pharynx.

Updated regimens for disseminated gonococcal infection, pelvic inflammatory disease, epididymitis, and gonococcal infections in patients with documented severe allergic reactions to penicillins or cephalosporins are available in separate documents at www.cdc.gov/std/treatment

Unless Chlamydia trachomatis has been specifically ruled out, all patients diagnosed with gonococcal disease should also be treated for possible coinfection, with a single dose of 1 g azithromycin by mouth or with 100 mg doxycycline twice a day by mouth for 7 days.

The full gonorrhea treatment guidelines are available at www.cdc.gov/?std/gonorrhea/arg

Test of cure is not routinely recommended, but patients with persistent or recurring symptoms following treatment should be reevaluated by culture for N. gonorrhoeae, and any positive isolates should undergo antimicrobial susceptibility testing.

Treatment failures or resistant gonococcal isolates should be reported to the CDC at 404-639-8373 through state and local public health authorities.

Specifics of the New Guidelines For Gonorrhea

Because of increased fluoroquinolone resistance of Neisseria gonorrhoeae in the United States, the Centers for Disease Control and Prevention no longer recommends the use of that class of antimicrobials for treatment of gonococcal infections in adolescent or adult patients, regardless of travel or sexual behavior.

The CDC's new guidelines include these recommendations:

▸ Uncomplicated gonococcal infections of the cervix, urethra, and rectum. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, or cefixime 400 mg in a single oral dose, plus treatment for chlamydia if chlamydial infection is not ruled out. Alternative regimens: Spectinomycin (not available in the United States) 2 g in a single dose IM or cephalosporin single-dose regimens (including ceftizoxime 500 mg IM, or cefoxitin 2 g IM administered with probenecid 1 g orally, or cefotaxime 500 mg IM).

▸ Uncomplicated gonococcal infections of the pharynx. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, plus treatment for chlamydia if chlamydial infection is not ruled out.

Fluoroquinolones should no longer be used for the treatment of gonorrhea in the United States, the Centers for Disease Control and Prevention has concluded.

The recommendation is based on new evidence suggesting that the prevalence of fluoroquinolone-resistant strains in the United States has now surpassed the prespecified threshold of 5%. Only one antimicrobial class—the cephalosporins—is now still recommended and available for the treatment of gonococcal infections or for other conditions that might be caused by Neisseria gonorrhoeae, such as pelvic inflammatory disease, the CDC said (MMWR 2007;56:332–6).

Fluoroquinolones have been used to treat gonorrhea since 1993. Between 1990 and 2001, the CDC's Gonococcal Isolate Surveillance Project (GISP) detected fluoroquinolone-resistant N. gonorrhoeae (QRNG) prevalences of less than 1% among urethral gonococcal isolates taken from males attending between 26 and 30 sexually transmitted disease clinics around the country.

But the prevalence rose to 2.2% in 2002, then to 4.1% in 2003, and to 6.8% in 2004. In 2005, 9.4% of 6,199 isolates collected by GISP were resistant to ciprofloxacin, and during January-June of 2006, 13.3% of 3,005 isolates were resistant.

“Gonorrhea has proven to be quite efficient at navigating around the drugs we use to combat it, developing resistance first to penicillin and tetracycline, and most recently to fluoroquinolones,” said Dr. John M. Douglas, director of the CDC's division of sexually transmitted diseases prevention, in a telebriefing held in conjunction with the release of the new guidelines.

Recommendations to stop the use of fluoroquinolones to treat gonorrhea had already been issued in 2000 for people who acquired their infections in Hawaii, and in 2002, the recommendation was extended to California.

In 2004, the CDC advised that fluoroquinolones should no longer be used to treat gonorrhea in men who have sex with men (MSM) throughout the United States. Excluding isolates from Hawaii and California, 6.1% of U.S. isolates in 2005 and 8.6% in 2006 were fluoroquinolone resistant, the CDC reported.

Data from GIST suggest that QRNG has been increasing among both MSM and heterosexual males since 2001. The prevalence among MSM, which was 1.6% in 2001, rose to 7.2% in 2002, 15% in 2003, 24% in 2004, and 29% in 2005. The increase has been slower among heterosexual males, from 0.9% in 2002 to 1.5% in 2003, 2.9% in 2004, and 3.8% in 2005.

Preliminary data from the first half of 2006 indicate that the QRNG prevalence was 38.3% among MSM and 6.7% among heterosexual males, with both numbers surpassing the 5% threshold set by both the CDC and the World Health Organization to ensure that all recommended gonorrhea treatments can be expected to cure 95% or more of infections, the CDC said.

Cephalosporins are now the only agents available in the United States that meet that standard. For the treatment of uncomplicated urogenital and anorectal gonorrhea, the CDC now recommends a single 125-mg intramuscular dose of ceftriaxone. A single oral 400-mg dose of cefixime is also recommended, but cefixime is available only in a suspension in the United States, not as 400-mg tablets.

Single oral doses of 400 mg cefpodoxime or 1 g cefuroxime axetil also are likely to be effective, but the data for those two regimens are more limited than for ceftriaxone, Dr. Douglas said during the briefing.

Alternative parenteral single-dose regimens for urogenital and anorectal gonorrhea include 500 mg ceftizoxime, 2 g cefoxitin with 1 g oral probenecid, or 500 mg cefotaxime.

However, these regimens don't offer any advantages over ceftriaxone, the CDC noted.

A single 125-mg dose of ceftriaxone also is the recommended treatment for uncomplicated gonococcal infections of the pharynx.

Updated regimens for disseminated gonococcal infection, pelvic inflammatory disease, epididymitis, and gonococcal infections in patients with documented severe allergic reactions to penicillins or cephalosporins are available in separate documents at www.cdc.gov/std/treatment

Unless Chlamydia trachomatis has been specifically ruled out, all patients diagnosed with gonococcal disease should also be treated for possible coinfection, with a single dose of 1 g azithromycin by mouth or with 100 mg doxycycline twice a day by mouth for 7 days.

The full gonorrhea treatment guidelines are available at www.cdc.gov/?std/gonorrhea/arg

Test of cure is not routinely recommended, but patients with persistent or recurring symptoms following treatment should be reevaluated by culture for N. gonorrhoeae, and any positive isolates should undergo antimicrobial susceptibility testing.

Treatment failures or resistant gonococcal isolates should be reported to the CDC at 404-639-8373 through state and local public health authorities.

Specifics of the New Guidelines For Gonorrhea

Because of increased fluoroquinolone resistance of Neisseria gonorrhoeae in the United States, the Centers for Disease Control and Prevention no longer recommends the use of that class of antimicrobials for treatment of gonococcal infections in adolescent or adult patients, regardless of travel or sexual behavior.

The CDC's new guidelines include these recommendations:

▸ Uncomplicated gonococcal infections of the cervix, urethra, and rectum. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, or cefixime 400 mg in a single oral dose, plus treatment for chlamydia if chlamydial infection is not ruled out. Alternative regimens: Spectinomycin (not available in the United States) 2 g in a single dose IM or cephalosporin single-dose regimens (including ceftizoxime 500 mg IM, or cefoxitin 2 g IM administered with probenecid 1 g orally, or cefotaxime 500 mg IM).

▸ Uncomplicated gonococcal infections of the pharynx. Recommended regimens: Ceftriaxone 125 mg in a single dose IM, plus treatment for chlamydia if chlamydial infection is not ruled out.

WASHINGTON — Routine HIV screening among all adults is cost effective even in settings where the prevalence is low, Dr. Rochelle P. Walensky said at a meeting on HIV diagnosis, prevention, and care in the United States.

But there's a catch. The cost-effectiveness of HIV screening relies heavily on effective linkage to care.

The costs and benefits of HIV screening are so strongly linked to subsequent care of identified HIV patients that the cost of the test itself—whether enzyme-linked immunoassay or rapid test technology is used—is much less relevant to the calculation, especially at prevalences above 1%, said Dr. Walensky, associate director of the Program in Epidemiology and Outcomes Research at the Harvard Center for AIDS Research, Boston.

She summarized cost-effectiveness data during the meeting, which was sponsored by the American Academy of HIV Medicine, along with other professional societies, the U.S. Department of Health and Human Services, and seven pharmaceutical and test kit manufacturers.

According to an analysis led by Dr. David Paltiel of Yale University, New Haven, Conn., the cost-effectiveness ratio for routine HIV screening every 5 years among high-risk patients (3.0% prevalence) in outpatient settings was $50,000 per quality-adjusted life year (QALY) gained. At a 1% prevalence of undiagnosed HIV infection, routine testing every 5 years had a cost-effectiveness ratio of $71,000/QALY gained (N. Engl. J. Med. 2005;352:586–95).

A separate study that was published in the same issue of the New England Journal of Medicine found a cost-effectiveness ratio of $41,736/QALY in a population with a 1% prevalence (N. Engl. J. Med. 2005;352:570–85).

In an updated analysis that included transmission effects in the model, Dr. Paltiel and his colleagues found that cost-effectiveness ratios remained below $50,000/QALY in settings with HIV prevalence as low as 0.2% for routine HIV screening on a one-time basis, and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years (Ann. Intern. Med. 2006;145:797–806).

By comparison, previous studies have found cost-effectiveness ratios of approximately $57,500/QALY for annual breast cancer screening in women aged 50–69 years, about $57,700 for colon cancer screening in adults aged 50–85 years, and $70,000 for diabetes screening in adults over age 25 years.

“HIV screening is more cost effective than other screening programs done routinely in the United States. … Taken together, these data strongly support the CDC guidelines,” said Dr. Walensky, who is also a practicing infectious disease specialist at Brigham and Women's and Massachusetts General hospitals, Boston.

An analysis for which she was the lead author suggested that in a setting of limited resources, it's better to target funds ensuring that people who are identified as HIV-positive return for follow-up than it is to offer screening to more people.

At an HIV prevalence of 1%, a program with a 20% probability of being tested and an 80% probability of follow-up yielded a cost-effectiveness ratio of $32,900/QALY, compared with $36,300 for a program with 80% testing but only 20% follow-up (Med. Decis. Making 2005;25:321–9).

“More simply put, we shouldn't be looking for more needles in a haystack if we're just going to throw them back,” Dr. Walensky said.

Another published analysis by Dr. Walensky and her colleagues dramatically illustrates the progress made over the years with the introduction of new interventions for AIDS patients, and why broader screening is now being encouraged: Back in 1989–1992, the introduction of opportunistic infection prophylaxis conferred a survival benefit of approximately 3.1 months/person, compared with untreated disease. The first wave of antiretroviral therapy in 1996 pushed that survival advantage up to 93.7 months.

Today, four eras of increasingly effective antiretroviral therapy in addition to prophylaxis has meant an extra 159.9 months of life, or 13 years beyond the life span of someone diagnosed in the mid-1980s.

“HIV diagnosis leads to therapies whose survival benefits are enormous,” Dr. Walensky said.

WASHINGTON — Routine HIV screening among all adults is cost effective even in settings where the prevalence is low, Dr. Rochelle P. Walensky said at a meeting on HIV diagnosis, prevention, and care in the United States.

But there's a catch. The cost-effectiveness of HIV screening relies heavily on effective linkage to care.

The costs and benefits of HIV screening are so strongly linked to subsequent care of identified HIV patients that the cost of the test itself—whether enzyme-linked immunoassay or rapid test technology is used—is much less relevant to the calculation, especially at prevalences above 1%, said Dr. Walensky, associate director of the Program in Epidemiology and Outcomes Research at the Harvard Center for AIDS Research, Boston.

She summarized cost-effectiveness data during the meeting, which was sponsored by the American Academy of HIV Medicine, along with other professional societies, the U.S. Department of Health and Human Services, and seven pharmaceutical and test kit manufacturers.

According to an analysis led by Dr. David Paltiel of Yale University, New Haven, Conn., the cost-effectiveness ratio for routine HIV screening every 5 years among high-risk patients (3.0% prevalence) in outpatient settings was $50,000 per quality-adjusted life year (QALY) gained. At a 1% prevalence of undiagnosed HIV infection, routine testing every 5 years had a cost-effectiveness ratio of $71,000/QALY gained (N. Engl. J. Med. 2005;352:586–95).

A separate study that was published in the same issue of the New England Journal of Medicine found a cost-effectiveness ratio of $41,736/QALY in a population with a 1% prevalence (N. Engl. J. Med. 2005;352:570–85).

In an updated analysis that included transmission effects in the model, Dr. Paltiel and his colleagues found that cost-effectiveness ratios remained below $50,000/QALY in settings with HIV prevalence as low as 0.2% for routine HIV screening on a one-time basis, and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years (Ann. Intern. Med. 2006;145:797–806).

By comparison, previous studies have found cost-effectiveness ratios of approximately $57,500/QALY for annual breast cancer screening in women aged 50–69 years, about $57,700 for colon cancer screening in adults aged 50–85 years, and $70,000 for diabetes screening in adults over age 25 years.

“HIV screening is more cost effective than other screening programs done routinely in the United States. … Taken together, these data strongly support the CDC guidelines,” said Dr. Walensky, who is also a practicing infectious disease specialist at Brigham and Women's and Massachusetts General hospitals, Boston.

An analysis for which she was the lead author suggested that in a setting of limited resources, it's better to target funds ensuring that people who are identified as HIV-positive return for follow-up than it is to offer screening to more people.

At an HIV prevalence of 1%, a program with a 20% probability of being tested and an 80% probability of follow-up yielded a cost-effectiveness ratio of $32,900/QALY, compared with $36,300 for a program with 80% testing but only 20% follow-up (Med. Decis. Making 2005;25:321–9).

“More simply put, we shouldn't be looking for more needles in a haystack if we're just going to throw them back,” Dr. Walensky said.

Another published analysis by Dr. Walensky and her colleagues dramatically illustrates the progress made over the years with the introduction of new interventions for AIDS patients, and why broader screening is now being encouraged: Back in 1989–1992, the introduction of opportunistic infection prophylaxis conferred a survival benefit of approximately 3.1 months/person, compared with untreated disease. The first wave of antiretroviral therapy in 1996 pushed that survival advantage up to 93.7 months.

Today, four eras of increasingly effective antiretroviral therapy in addition to prophylaxis has meant an extra 159.9 months of life, or 13 years beyond the life span of someone diagnosed in the mid-1980s.

“HIV diagnosis leads to therapies whose survival benefits are enormous,” Dr. Walensky said.

WASHINGTON — Routine HIV screening among all adults is cost effective even in settings where the prevalence is low, Dr. Rochelle P. Walensky said at a meeting on HIV diagnosis, prevention, and care in the United States.

But there's a catch. The cost-effectiveness of HIV screening relies heavily on effective linkage to care.

The costs and benefits of HIV screening are so strongly linked to subsequent care of identified HIV patients that the cost of the test itself—whether enzyme-linked immunoassay or rapid test technology is used—is much less relevant to the calculation, especially at prevalences above 1%, said Dr. Walensky, associate director of the Program in Epidemiology and Outcomes Research at the Harvard Center for AIDS Research, Boston.

She summarized cost-effectiveness data during the meeting, which was sponsored by the American Academy of HIV Medicine, along with other professional societies, the U.S. Department of Health and Human Services, and seven pharmaceutical and test kit manufacturers.

According to an analysis led by Dr. David Paltiel of Yale University, New Haven, Conn., the cost-effectiveness ratio for routine HIV screening every 5 years among high-risk patients (3.0% prevalence) in outpatient settings was $50,000 per quality-adjusted life year (QALY) gained. At a 1% prevalence of undiagnosed HIV infection, routine testing every 5 years had a cost-effectiveness ratio of $71,000/QALY gained (N. Engl. J. Med. 2005;352:586–95).

A separate study that was published in the same issue of the New England Journal of Medicine found a cost-effectiveness ratio of $41,736/QALY in a population with a 1% prevalence (N. Engl. J. Med. 2005;352:570–85).

In an updated analysis that included transmission effects in the model, Dr. Paltiel and his colleagues found that cost-effectiveness ratios remained below $50,000/QALY in settings with HIV prevalence as low as 0.2% for routine HIV screening on a one-time basis, and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years (Ann. Intern. Med. 2006;145:797–806).

By comparison, previous studies have found cost-effectiveness ratios of approximately $57,500/QALY for annual breast cancer screening in women aged 50–69 years, about $57,700 for colon cancer screening in adults aged 50–85 years, and $70,000 for diabetes screening in adults over age 25 years.

“HIV screening is more cost effective than other screening programs done routinely in the United States. … Taken together, these data strongly support the CDC guidelines,” said Dr. Walensky, who is also a practicing infectious disease specialist at Brigham and Women's and Massachusetts General hospitals, Boston.

An analysis for which she was the lead author suggested that in a setting of limited resources, it's better to target funds ensuring that people who are identified as HIV-positive return for follow-up than it is to offer screening to more people.

At an HIV prevalence of 1%, a program with a 20% probability of being tested and an 80% probability of follow-up yielded a cost-effectiveness ratio of $32,900/QALY, compared with $36,300 for a program with 80% testing but only 20% follow-up (Med. Decis. Making 2005;25:321–9).

“More simply put, we shouldn't be looking for more needles in a haystack if we're just going to throw them back,” Dr. Walensky said.

Another published analysis by Dr. Walensky and her colleagues dramatically illustrates the progress made over the years with the introduction of new interventions for AIDS patients, and why broader screening is now being encouraged: Back in 1989–1992, the introduction of opportunistic infection prophylaxis conferred a survival benefit of approximately 3.1 months/person, compared with untreated disease. The first wave of antiretroviral therapy in 1996 pushed that survival advantage up to 93.7 months.

Today, four eras of increasingly effective antiretroviral therapy in addition to prophylaxis has meant an extra 159.9 months of life, or 13 years beyond the life span of someone diagnosed in the mid-1980s.

“HIV diagnosis leads to therapies whose survival benefits are enormous,” Dr. Walensky said.

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women.

Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure.

Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective.

It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV. The company plans to present those data later this year.

“The preliminary results are quite encouraging,” Dr. Barr commented.

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women.

Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure.

Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective.

It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV. The company plans to present those data later this year.

“The preliminary results are quite encouraging,” Dr. Barr commented.

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women.

Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure.

Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective.

It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV. The company plans to present those data later this year.

“The preliminary results are quite encouraging,” Dr. Barr commented.