Miriam E. Tucker

WASHINGTON — Preliminary data from an ongoing observational study suggest no safety concerns associated with the use of tacrolimus ointment for the treatment of atopic dermatitis in children, Dr. M. Joyce Rico reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

“The data to date confirm the established safety profile of tacrolimus ointment,” said Dr. Rico, vice president of research and development at Astellas Pharma US, Inc.

In March 2005, concerns about possible malignancy prompted the Food and Drug Administration to add a boxed warning to the product labels of tacrolimus (Protopic) and to pimecrolimus (Elidel), advising physicians that the two topical nonsteroidal immune suppressants should be used only as directed and only as second-line therapy after other treatments have failed.

Two months later, Astellas began enrolling patients in a phase IV prospective study to evaluate the long-term safety of tacrolimus ointment in patients who first began using it for the treatment of atopic dermatitis prior to age 16 years, for a minimum of 6 weeks (either continuously or intermittently). Patients are being followed for 10 years with annual physical examinations and dermatologic examinations every 2 years, along with phone calls twice a year to collect additional safety information.

The planned study enrollment is 8,000 patients. Although tacrolimus ointment is indicated for the treatment of moderate to severe atopic dermatitis in nonimmunocompromised children aged 2 years and older, data are being collected on “actual use” conditions, including off-label use in children under 2 years of age.

To date, 1,779 patients from the United States, Germany, Ireland, and the United Kingdom have been enrolled. They are 52% female and 48% male, with a median age of 4 years at the time of first tacrolimus exposure and 6 years at study enrollment. Of note, 24% were first exposed to tacrolimus before 2 years of age, contrary to the package labeling, Dr. Rico remarked.

At the time of study enrollment, severity of atopic dermatitis was moderate in 41%, severe in 12%, not currently active in 6%, and mild in 41%. Not all of the latter two groups constituted off-label use, since some of those with mild or inactive disease may have had moderate to severe disease at the time they began using the ointment.

The median cumulative duration of tacrolimus ointment use was 1.9 patient-years, with a median 9.0 months of actual usage. Less than half of the patients (44%) were using the 0.03% concentration, the only one approved for use in children aged 2–15 years; the other 56% were using the 0.1% formulation, which is approved for adults only. At baseline, 70% of the study population was currently using the ointment.

Data were also collected on the patients' use of pimecrolimus cream, for which the median cumulative duration of use was 2.2 patient-years, with a median 4 actual months of usage. At baseline, 19% of the patients were currently applying pimecrolimus, Dr. Rico reported.

Before enrollment, three patients reported a history of malignancy, including one neuroblastoma and two leukemias. However, no malignancies have been reported since study enrollment. Among the serious adverse events reported so far were pneumonia and asthma-associated bronchitis in one patient, cellulitis in another, viral gastroenteritis in a third, and anaphylaxis in a fourth. All events were deemed by the investigators to be “not related” or “unlikely” to be related to the tacrolimus ointment.

Dr. Rico appealed to the dermatologic community to assist in enrolling patients into this study. “To be able to address this important issue, we need to enroll 8,000 patients. … We're trying to make this very user friendly for both patients and physicians.” For more information, the number to call is 877-277-7530.

WASHINGTON — Preliminary data from an ongoing observational study suggest no safety concerns associated with the use of tacrolimus ointment for the treatment of atopic dermatitis in children, Dr. M. Joyce Rico reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

“The data to date confirm the established safety profile of tacrolimus ointment,” said Dr. Rico, vice president of research and development at Astellas Pharma US, Inc.

In March 2005, concerns about possible malignancy prompted the Food and Drug Administration to add a boxed warning to the product labels of tacrolimus (Protopic) and to pimecrolimus (Elidel), advising physicians that the two topical nonsteroidal immune suppressants should be used only as directed and only as second-line therapy after other treatments have failed.

Two months later, Astellas began enrolling patients in a phase IV prospective study to evaluate the long-term safety of tacrolimus ointment in patients who first began using it for the treatment of atopic dermatitis prior to age 16 years, for a minimum of 6 weeks (either continuously or intermittently). Patients are being followed for 10 years with annual physical examinations and dermatologic examinations every 2 years, along with phone calls twice a year to collect additional safety information.

The planned study enrollment is 8,000 patients. Although tacrolimus ointment is indicated for the treatment of moderate to severe atopic dermatitis in nonimmunocompromised children aged 2 years and older, data are being collected on “actual use” conditions, including off-label use in children under 2 years of age.

To date, 1,779 patients from the United States, Germany, Ireland, and the United Kingdom have been enrolled. They are 52% female and 48% male, with a median age of 4 years at the time of first tacrolimus exposure and 6 years at study enrollment. Of note, 24% were first exposed to tacrolimus before 2 years of age, contrary to the package labeling, Dr. Rico remarked.

At the time of study enrollment, severity of atopic dermatitis was moderate in 41%, severe in 12%, not currently active in 6%, and mild in 41%. Not all of the latter two groups constituted off-label use, since some of those with mild or inactive disease may have had moderate to severe disease at the time they began using the ointment.

The median cumulative duration of tacrolimus ointment use was 1.9 patient-years, with a median 9.0 months of actual usage. Less than half of the patients (44%) were using the 0.03% concentration, the only one approved for use in children aged 2–15 years; the other 56% were using the 0.1% formulation, which is approved for adults only. At baseline, 70% of the study population was currently using the ointment.

Data were also collected on the patients' use of pimecrolimus cream, for which the median cumulative duration of use was 2.2 patient-years, with a median 4 actual months of usage. At baseline, 19% of the patients were currently applying pimecrolimus, Dr. Rico reported.

Before enrollment, three patients reported a history of malignancy, including one neuroblastoma and two leukemias. However, no malignancies have been reported since study enrollment. Among the serious adverse events reported so far were pneumonia and asthma-associated bronchitis in one patient, cellulitis in another, viral gastroenteritis in a third, and anaphylaxis in a fourth. All events were deemed by the investigators to be “not related” or “unlikely” to be related to the tacrolimus ointment.

Dr. Rico appealed to the dermatologic community to assist in enrolling patients into this study. “To be able to address this important issue, we need to enroll 8,000 patients. … We're trying to make this very user friendly for both patients and physicians.” For more information, the number to call is 877-277-7530.

WASHINGTON — Preliminary data from an ongoing observational study suggest no safety concerns associated with the use of tacrolimus ointment for the treatment of atopic dermatitis in children, Dr. M. Joyce Rico reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

“The data to date confirm the established safety profile of tacrolimus ointment,” said Dr. Rico, vice president of research and development at Astellas Pharma US, Inc.

In March 2005, concerns about possible malignancy prompted the Food and Drug Administration to add a boxed warning to the product labels of tacrolimus (Protopic) and to pimecrolimus (Elidel), advising physicians that the two topical nonsteroidal immune suppressants should be used only as directed and only as second-line therapy after other treatments have failed.

Two months later, Astellas began enrolling patients in a phase IV prospective study to evaluate the long-term safety of tacrolimus ointment in patients who first began using it for the treatment of atopic dermatitis prior to age 16 years, for a minimum of 6 weeks (either continuously or intermittently). Patients are being followed for 10 years with annual physical examinations and dermatologic examinations every 2 years, along with phone calls twice a year to collect additional safety information.

The planned study enrollment is 8,000 patients. Although tacrolimus ointment is indicated for the treatment of moderate to severe atopic dermatitis in nonimmunocompromised children aged 2 years and older, data are being collected on “actual use” conditions, including off-label use in children under 2 years of age.

To date, 1,779 patients from the United States, Germany, Ireland, and the United Kingdom have been enrolled. They are 52% female and 48% male, with a median age of 4 years at the time of first tacrolimus exposure and 6 years at study enrollment. Of note, 24% were first exposed to tacrolimus before 2 years of age, contrary to the package labeling, Dr. Rico remarked.

At the time of study enrollment, severity of atopic dermatitis was moderate in 41%, severe in 12%, not currently active in 6%, and mild in 41%. Not all of the latter two groups constituted off-label use, since some of those with mild or inactive disease may have had moderate to severe disease at the time they began using the ointment.

The median cumulative duration of tacrolimus ointment use was 1.9 patient-years, with a median 9.0 months of actual usage. Less than half of the patients (44%) were using the 0.03% concentration, the only one approved for use in children aged 2–15 years; the other 56% were using the 0.1% formulation, which is approved for adults only. At baseline, 70% of the study population was currently using the ointment.

Data were also collected on the patients' use of pimecrolimus cream, for which the median cumulative duration of use was 2.2 patient-years, with a median 4 actual months of usage. At baseline, 19% of the patients were currently applying pimecrolimus, Dr. Rico reported.

Before enrollment, three patients reported a history of malignancy, including one neuroblastoma and two leukemias. However, no malignancies have been reported since study enrollment. Among the serious adverse events reported so far were pneumonia and asthma-associated bronchitis in one patient, cellulitis in another, viral gastroenteritis in a third, and anaphylaxis in a fourth. All events were deemed by the investigators to be “not related” or “unlikely” to be related to the tacrolimus ointment.

Dr. Rico appealed to the dermatologic community to assist in enrolling patients into this study. “To be able to address this important issue, we need to enroll 8,000 patients. … We're trying to make this very user friendly for both patients and physicians.” For more information, the number to call is 877-277-7530.

Diagnosis: Spiny Keratoderma

STOWE, VT. — The differential diagnosis for this patient included punctate porokeratosis, verruca vulgaris, pitted keratolysis, arsenical keratoses, and genetic disorders such as Darier's disease and Cowden disease that can cause keratotic lesions, Dr. Jamie A. Alpert said at a dermatology conference sponsored by the University of Vermont.

Histologic features of her lesions included a discrete, compact parakeratotic column with slight epidermal invagination that was contiguous with the granular layer and easily differentiated from the adjacent orthokeratotic layer. The epidermis was otherwise unremarkable, and there was no appreciable inflammation.

The diagnosis was spiny keratoderma, an autosomal dominant condition characterized by numerous tiny keratotic projections that resemble the spines on the rotating drum inside a music box. The disorder can be palmoplantar or generalized and is associated with malignancy in a subset of patients, said Dr. Alpert of the University of Vermont, Burlington.

Many reports of palmoplantar punctate keratotic projections have appeared in the literature, dating back to 1971. In addition to the name spiny keratoderma, these lesions also have been called punctate keratoderma, punctate porokeratosis, palmoplantar keratosis acuminatum, and palmoplantar filiform hyperkeratosis.

Broad classification of palmoplantar punctate keratotic lesions is based on morphology, distribution, and whether they are acquired or inherited.

In 1994, Dr. Thomas W. McGovern devised a classification scheme specifically for spiny keratoderma (SK), which he nicknamed "music box spine dermatoses." He divided the various presentations into five groups, based on location and histology:

▸ 1a: Palmoplantar parakeratotic SK, involving predominantly the palms and/or soles, with histology showing the parakeratotic column. The patient had this type.

▸ 1b: Disseminated parakeratotic SK, which is widespread with general palmoplantar sparing, with the same parakeratotic column as is seen in the palmoplantar parakeratotic type.

▸ 2a: Palmoplantar orthokeratotic SK, involving predominantly the palms and/or soles and showing orthokeratotic hyperkeratosis on histology.

▸ 2b: Disseminated orthokeratotic SK, widespread with general palmoplantar sparing and with histology showing orthokeratotic hyperkeratosis.

▸ 3: SK in eccrine hamartoma, which can occur on any cutaneous surface and shows a column of parakeratosis associated with skin appendages on histology.

Treatment is difficult. Lanolin and petrolatum-containing moisturizer may provide some relief. A variety of other agents have been tried, including topical ammonium lactate, retinoids, glycolic acid peel, 5-fluorouracil cream, and 6% salicylic acid (usually under occlusion), as well as electrodesiccation and mechanical removal.

"They all work to some degree, but it always comes back," Dr. Alpert said.

An age-appropriate malignancy work-up should be considered in all patients with new onset of SK and widely distributed lesions. This patient underwent a complete blood count with differential, metabolic panel, lactic dehydrogenase, chest x-ray, mammogram, and colonoscopy. No internal cancers were identified.

Treatment with 40% urea cream smoothed out her lesions, and she has not been seen since February 2006.

Should she return with recurrence, the plan is to try tazarotene gel or use a Dremel tool to sand down the lesions, Dr. Alpert said in an interview.

Courtesy Dr. Deborah L. Cook

Diagnosis: Spiny Keratoderma

STOWE, VT. — The differential diagnosis for this patient included punctate porokeratosis, verruca vulgaris, pitted keratolysis, arsenical keratoses, and genetic disorders such as Darier's disease and Cowden disease that can cause keratotic lesions, Dr. Jamie A. Alpert said at a dermatology conference sponsored by the University of Vermont.

Histologic features of her lesions included a discrete, compact parakeratotic column with slight epidermal invagination that was contiguous with the granular layer and easily differentiated from the adjacent orthokeratotic layer. The epidermis was otherwise unremarkable, and there was no appreciable inflammation.

The diagnosis was spiny keratoderma, an autosomal dominant condition characterized by numerous tiny keratotic projections that resemble the spines on the rotating drum inside a music box. The disorder can be palmoplantar or generalized and is associated with malignancy in a subset of patients, said Dr. Alpert of the University of Vermont, Burlington.

Many reports of palmoplantar punctate keratotic projections have appeared in the literature, dating back to 1971. In addition to the name spiny keratoderma, these lesions also have been called punctate keratoderma, punctate porokeratosis, palmoplantar keratosis acuminatum, and palmoplantar filiform hyperkeratosis.

Broad classification of palmoplantar punctate keratotic lesions is based on morphology, distribution, and whether they are acquired or inherited.

In 1994, Dr. Thomas W. McGovern devised a classification scheme specifically for spiny keratoderma (SK), which he nicknamed "music box spine dermatoses." He divided the various presentations into five groups, based on location and histology:

▸ 1a: Palmoplantar parakeratotic SK, involving predominantly the palms and/or soles, with histology showing the parakeratotic column. The patient had this type.

▸ 1b: Disseminated parakeratotic SK, which is widespread with general palmoplantar sparing, with the same parakeratotic column as is seen in the palmoplantar parakeratotic type.

▸ 2a: Palmoplantar orthokeratotic SK, involving predominantly the palms and/or soles and showing orthokeratotic hyperkeratosis on histology.

▸ 2b: Disseminated orthokeratotic SK, widespread with general palmoplantar sparing and with histology showing orthokeratotic hyperkeratosis.

▸ 3: SK in eccrine hamartoma, which can occur on any cutaneous surface and shows a column of parakeratosis associated with skin appendages on histology.

Treatment is difficult. Lanolin and petrolatum-containing moisturizer may provide some relief. A variety of other agents have been tried, including topical ammonium lactate, retinoids, glycolic acid peel, 5-fluorouracil cream, and 6% salicylic acid (usually under occlusion), as well as electrodesiccation and mechanical removal.

"They all work to some degree, but it always comes back," Dr. Alpert said.

An age-appropriate malignancy work-up should be considered in all patients with new onset of SK and widely distributed lesions. This patient underwent a complete blood count with differential, metabolic panel, lactic dehydrogenase, chest x-ray, mammogram, and colonoscopy. No internal cancers were identified.

Treatment with 40% urea cream smoothed out her lesions, and she has not been seen since February 2006.

Should she return with recurrence, the plan is to try tazarotene gel or use a Dremel tool to sand down the lesions, Dr. Alpert said in an interview.

Courtesy Dr. Deborah L. Cook

Diagnosis: Spiny Keratoderma

STOWE, VT. — The differential diagnosis for this patient included punctate porokeratosis, verruca vulgaris, pitted keratolysis, arsenical keratoses, and genetic disorders such as Darier's disease and Cowden disease that can cause keratotic lesions, Dr. Jamie A. Alpert said at a dermatology conference sponsored by the University of Vermont.

Histologic features of her lesions included a discrete, compact parakeratotic column with slight epidermal invagination that was contiguous with the granular layer and easily differentiated from the adjacent orthokeratotic layer. The epidermis was otherwise unremarkable, and there was no appreciable inflammation.

The diagnosis was spiny keratoderma, an autosomal dominant condition characterized by numerous tiny keratotic projections that resemble the spines on the rotating drum inside a music box. The disorder can be palmoplantar or generalized and is associated with malignancy in a subset of patients, said Dr. Alpert of the University of Vermont, Burlington.

Many reports of palmoplantar punctate keratotic projections have appeared in the literature, dating back to 1971. In addition to the name spiny keratoderma, these lesions also have been called punctate keratoderma, punctate porokeratosis, palmoplantar keratosis acuminatum, and palmoplantar filiform hyperkeratosis.

Broad classification of palmoplantar punctate keratotic lesions is based on morphology, distribution, and whether they are acquired or inherited.

In 1994, Dr. Thomas W. McGovern devised a classification scheme specifically for spiny keratoderma (SK), which he nicknamed "music box spine dermatoses." He divided the various presentations into five groups, based on location and histology:

▸ 1a: Palmoplantar parakeratotic SK, involving predominantly the palms and/or soles, with histology showing the parakeratotic column. The patient had this type.

▸ 1b: Disseminated parakeratotic SK, which is widespread with general palmoplantar sparing, with the same parakeratotic column as is seen in the palmoplantar parakeratotic type.

▸ 2a: Palmoplantar orthokeratotic SK, involving predominantly the palms and/or soles and showing orthokeratotic hyperkeratosis on histology.

▸ 2b: Disseminated orthokeratotic SK, widespread with general palmoplantar sparing and with histology showing orthokeratotic hyperkeratosis.

▸ 3: SK in eccrine hamartoma, which can occur on any cutaneous surface and shows a column of parakeratosis associated with skin appendages on histology.

Treatment is difficult. Lanolin and petrolatum-containing moisturizer may provide some relief. A variety of other agents have been tried, including topical ammonium lactate, retinoids, glycolic acid peel, 5-fluorouracil cream, and 6% salicylic acid (usually under occlusion), as well as electrodesiccation and mechanical removal.

"They all work to some degree, but it always comes back," Dr. Alpert said.

An age-appropriate malignancy work-up should be considered in all patients with new onset of SK and widely distributed lesions. This patient underwent a complete blood count with differential, metabolic panel, lactic dehydrogenase, chest x-ray, mammogram, and colonoscopy. No internal cancers were identified.

Treatment with 40% urea cream smoothed out her lesions, and she has not been seen since February 2006.

Should she return with recurrence, the plan is to try tazarotene gel or use a Dremel tool to sand down the lesions, Dr. Alpert said in an interview.

Courtesy Dr. Deborah L. Cook

STOWE, VT. — A “striking” erythematous, peeling eruption of the distal extremities associated with a new cancer drug will be seen increasingly in physicians' offices, Dr. Peter W. Heald predicted at a dermatology conference sponsored by the University of Vermont.

The drug, sorafenib, was approved in 2005 for the treatment of advanced renal cell carcinoma. Codeveloped by Bayer Pharmaceuticals and Onyx Pharmaceuticals Inc. under the name Nexavar, the agent is a multikinase inhibitor of tumor-cell proliferation and angiogenesis. It is currently being evaluated for a variety of other tumors, including melanoma.

In the meantime, some patients with advanced melanoma who are unable to tolerate interferon have been treated with the oral medication. “This is being used off-label for melanoma, even though the melanoma trials are still in progress at this point,” said Dr. Heald, professor of dermatology at Yale University, New Haven, Conn.

A recently published phase III randomized, double-blind placebo-controlled trial of oral sorafenib (400 mg twice daily) in 903 patients with advanced clear-cell renal cell carcinoma demonstrated a significant increase in progression-free survival (5.5 months vs. 2.8 months). However, the treatment was associated with a variety of adverse effects, including the hand-foot skin reaction in 30% of the patients (median treatment duration 23 weeks), compared with just 7% (median 12 weeks) in the placebo group (N. Engl. J. Med. 2007;356:125–34).

“If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up. Now that the drug is on the market, off-label use will increase along with its use in management of renal cell carcinoma,” said Dr. Heald, who is also attending dermatologist at the West Haven (Conn.) VA Medical Center.

Most of the literature on sorafenib hand-foot syndrome comes from the oncology community and is “a little murky at the moment,” he said.

The eruption presents in a spectrum ranging from peeling to bullae and erosions, and also appears to have a vascular component. In one case report, the authors described what they considered to be “leukocytoclastic vasculitis masquerading as hand-foot syndrome” in a 70-year-old man with metastatic lung cancer who was taking sorafenib (Arch. Dermatol. 2006;142:1510–1).

But Dr. Heald says he believes that the vascular component is part of the spectrum of sorafenib hand-foot syndrome, describing one of his patients with venous insufficiency in whom the skin manifestation of the syndrome was worse in the more severely affected limb.

The syndrome does appear to be dose dependent. In a pooled analysis of four phase I dose-escalation trials of sorafenib, few patients experienced it at dosages less than 300 mg twice daily, but both frequency and severity of the skin eruption increased with dosages of 300–600 mg b.i.d. At the recommended dosage of 400 mg b.i.d., 15% of patients experienced hand-foot syndrome of grade 2 or 3 (Eur. J. Cancer 2006;42:548–56).

As with the drug eruptions that occur with epidermal growth factor inhibitors such as cetuximab and erlotinib, the patients who experienced sorafenib hand-foot syndrome had significantly longer times to progression than did those who did not experience the skin toxicity.

Some oncologists believe that the sorafenib-associated syndrome is the same as the drug eruption known as “Ara-C syndrome,” a painful erythematous palmar/plantar eruption seen in leukemia patients receiving intravenous treatment with cytosine arabinoside (Ara-C).

Dr. Heald disagreed, though, noting that Ara-C syndrome doesn't cause the “funky split peeling” that is worse distally and improves farther up the limb, basically disappearing above the elbow or knee.

Treatment of sorafenib hand-foot syndrome depends on its severity. Topical steroids to minimize the peeling usually suffice for patients with grade 1 disease involving minimal erythema. Topical steroids should also be tried first in patients with grade 2 disease, defined as peeling, bullae, and edema that don't interfere with activities of daily living. Keratinolytic agents such as urea may be helpful in these patients as well, he said.

But for patients with grade 2 disease that is refractory to topical steroids and for those with grade 3 disease that interferes with activities of daily living, Dr. Heald recommended working with the patient's oncologist to interrupt the sorafenib therapy and restart it at a lower dose. In the published phase III trial, doses were reduced in 13% and interrupted in 21% of the sorafenib group because of adverse events, most of which were due to hand-foot skin reactions or gastrointestinal events.

As the off-label use of sorafenib increases for the treatment of a variety of cancers, physicians will be seeing increasing numbers of patients taking the drug. In addition to the hand-foot syndrome, 40% of the patients in the phase III trial experienced rash/desquamation, 27% had alopecia, and 19% had pruritus, compared with 2% or less of those adverse events in the placebo group.

Currently, investigators are looking at additional uses for sorafenib. One published phase II study involving 37 patients with advanced melanoma found little or no antitumor activity with 400 mg b.i.d. sorafenib monotherapy (Brit. J. Cancer 2006;95:581–6), and a manufacturer-funded, phase II randomized trial of sorafenib or placebo in combination with carboplatin and paclitaxel as second-line therapy in 277 patients with advanced melanoma failed to reach its primary end point of progression-free survival.

Bayer and Onyx, however, are continuing to investigate the drug's use in melanoma. An ongoing phase II study using sorafenib in combination with dacarbazine as first-line therapy has thus far shown a 50% improvement in progression-free survival, Onyx spokesperson Julie Wood said in an interview.

At the same time, at least two other externally sponsored phase II studies are also looking at combination therapy with sorafenib in treating melanoma. Other trials are investigating its use for liver, lung, and breast cancer, she said.

In any case, Dr. Heald noted, “As use of this drug spreads out from renal cell carcinoma, we'll be seeing more and more hand-foot syndrome.”

'If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up.' DR. HEALD

Grade 2 hand-foot syndrome, causing peeling on the plantar surface, is shown on a man who took sorafenib for 2 months.

Grade 3 syndrome appeared as hemorrhagic, pustular acral lesions on the hands of this patient who needed a lower dose. Photos courtesy Dr. Peter W. Heald

STOWE, VT. — A “striking” erythematous, peeling eruption of the distal extremities associated with a new cancer drug will be seen increasingly in physicians' offices, Dr. Peter W. Heald predicted at a dermatology conference sponsored by the University of Vermont.

The drug, sorafenib, was approved in 2005 for the treatment of advanced renal cell carcinoma. Codeveloped by Bayer Pharmaceuticals and Onyx Pharmaceuticals Inc. under the name Nexavar, the agent is a multikinase inhibitor of tumor-cell proliferation and angiogenesis. It is currently being evaluated for a variety of other tumors, including melanoma.

In the meantime, some patients with advanced melanoma who are unable to tolerate interferon have been treated with the oral medication. “This is being used off-label for melanoma, even though the melanoma trials are still in progress at this point,” said Dr. Heald, professor of dermatology at Yale University, New Haven, Conn.

A recently published phase III randomized, double-blind placebo-controlled trial of oral sorafenib (400 mg twice daily) in 903 patients with advanced clear-cell renal cell carcinoma demonstrated a significant increase in progression-free survival (5.5 months vs. 2.8 months). However, the treatment was associated with a variety of adverse effects, including the hand-foot skin reaction in 30% of the patients (median treatment duration 23 weeks), compared with just 7% (median 12 weeks) in the placebo group (N. Engl. J. Med. 2007;356:125–34).

“If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up. Now that the drug is on the market, off-label use will increase along with its use in management of renal cell carcinoma,” said Dr. Heald, who is also attending dermatologist at the West Haven (Conn.) VA Medical Center.

Most of the literature on sorafenib hand-foot syndrome comes from the oncology community and is “a little murky at the moment,” he said.

The eruption presents in a spectrum ranging from peeling to bullae and erosions, and also appears to have a vascular component. In one case report, the authors described what they considered to be “leukocytoclastic vasculitis masquerading as hand-foot syndrome” in a 70-year-old man with metastatic lung cancer who was taking sorafenib (Arch. Dermatol. 2006;142:1510–1).

But Dr. Heald says he believes that the vascular component is part of the spectrum of sorafenib hand-foot syndrome, describing one of his patients with venous insufficiency in whom the skin manifestation of the syndrome was worse in the more severely affected limb.

The syndrome does appear to be dose dependent. In a pooled analysis of four phase I dose-escalation trials of sorafenib, few patients experienced it at dosages less than 300 mg twice daily, but both frequency and severity of the skin eruption increased with dosages of 300–600 mg b.i.d. At the recommended dosage of 400 mg b.i.d., 15% of patients experienced hand-foot syndrome of grade 2 or 3 (Eur. J. Cancer 2006;42:548–56).

As with the drug eruptions that occur with epidermal growth factor inhibitors such as cetuximab and erlotinib, the patients who experienced sorafenib hand-foot syndrome had significantly longer times to progression than did those who did not experience the skin toxicity.

Some oncologists believe that the sorafenib-associated syndrome is the same as the drug eruption known as “Ara-C syndrome,” a painful erythematous palmar/plantar eruption seen in leukemia patients receiving intravenous treatment with cytosine arabinoside (Ara-C).

Dr. Heald disagreed, though, noting that Ara-C syndrome doesn't cause the “funky split peeling” that is worse distally and improves farther up the limb, basically disappearing above the elbow or knee.

Treatment of sorafenib hand-foot syndrome depends on its severity. Topical steroids to minimize the peeling usually suffice for patients with grade 1 disease involving minimal erythema. Topical steroids should also be tried first in patients with grade 2 disease, defined as peeling, bullae, and edema that don't interfere with activities of daily living. Keratinolytic agents such as urea may be helpful in these patients as well, he said.

But for patients with grade 2 disease that is refractory to topical steroids and for those with grade 3 disease that interferes with activities of daily living, Dr. Heald recommended working with the patient's oncologist to interrupt the sorafenib therapy and restart it at a lower dose. In the published phase III trial, doses were reduced in 13% and interrupted in 21% of the sorafenib group because of adverse events, most of which were due to hand-foot skin reactions or gastrointestinal events.

As the off-label use of sorafenib increases for the treatment of a variety of cancers, physicians will be seeing increasing numbers of patients taking the drug. In addition to the hand-foot syndrome, 40% of the patients in the phase III trial experienced rash/desquamation, 27% had alopecia, and 19% had pruritus, compared with 2% or less of those adverse events in the placebo group.

Currently, investigators are looking at additional uses for sorafenib. One published phase II study involving 37 patients with advanced melanoma found little or no antitumor activity with 400 mg b.i.d. sorafenib monotherapy (Brit. J. Cancer 2006;95:581–6), and a manufacturer-funded, phase II randomized trial of sorafenib or placebo in combination with carboplatin and paclitaxel as second-line therapy in 277 patients with advanced melanoma failed to reach its primary end point of progression-free survival.

Bayer and Onyx, however, are continuing to investigate the drug's use in melanoma. An ongoing phase II study using sorafenib in combination with dacarbazine as first-line therapy has thus far shown a 50% improvement in progression-free survival, Onyx spokesperson Julie Wood said in an interview.

At the same time, at least two other externally sponsored phase II studies are also looking at combination therapy with sorafenib in treating melanoma. Other trials are investigating its use for liver, lung, and breast cancer, she said.

In any case, Dr. Heald noted, “As use of this drug spreads out from renal cell carcinoma, we'll be seeing more and more hand-foot syndrome.”

'If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up.' DR. HEALD

Grade 2 hand-foot syndrome, causing peeling on the plantar surface, is shown on a man who took sorafenib for 2 months.

Grade 3 syndrome appeared as hemorrhagic, pustular acral lesions on the hands of this patient who needed a lower dose. Photos courtesy Dr. Peter W. Heald

STOWE, VT. — A “striking” erythematous, peeling eruption of the distal extremities associated with a new cancer drug will be seen increasingly in physicians' offices, Dr. Peter W. Heald predicted at a dermatology conference sponsored by the University of Vermont.

The drug, sorafenib, was approved in 2005 for the treatment of advanced renal cell carcinoma. Codeveloped by Bayer Pharmaceuticals and Onyx Pharmaceuticals Inc. under the name Nexavar, the agent is a multikinase inhibitor of tumor-cell proliferation and angiogenesis. It is currently being evaluated for a variety of other tumors, including melanoma.

In the meantime, some patients with advanced melanoma who are unable to tolerate interferon have been treated with the oral medication. “This is being used off-label for melanoma, even though the melanoma trials are still in progress at this point,” said Dr. Heald, professor of dermatology at Yale University, New Haven, Conn.

A recently published phase III randomized, double-blind placebo-controlled trial of oral sorafenib (400 mg twice daily) in 903 patients with advanced clear-cell renal cell carcinoma demonstrated a significant increase in progression-free survival (5.5 months vs. 2.8 months). However, the treatment was associated with a variety of adverse effects, including the hand-foot skin reaction in 30% of the patients (median treatment duration 23 weeks), compared with just 7% (median 12 weeks) in the placebo group (N. Engl. J. Med. 2007;356:125–34).

“If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up. Now that the drug is on the market, off-label use will increase along with its use in management of renal cell carcinoma,” said Dr. Heald, who is also attending dermatologist at the West Haven (Conn.) VA Medical Center.

Most of the literature on sorafenib hand-foot syndrome comes from the oncology community and is “a little murky at the moment,” he said.

The eruption presents in a spectrum ranging from peeling to bullae and erosions, and also appears to have a vascular component. In one case report, the authors described what they considered to be “leukocytoclastic vasculitis masquerading as hand-foot syndrome” in a 70-year-old man with metastatic lung cancer who was taking sorafenib (Arch. Dermatol. 2006;142:1510–1).

But Dr. Heald says he believes that the vascular component is part of the spectrum of sorafenib hand-foot syndrome, describing one of his patients with venous insufficiency in whom the skin manifestation of the syndrome was worse in the more severely affected limb.

The syndrome does appear to be dose dependent. In a pooled analysis of four phase I dose-escalation trials of sorafenib, few patients experienced it at dosages less than 300 mg twice daily, but both frequency and severity of the skin eruption increased with dosages of 300–600 mg b.i.d. At the recommended dosage of 400 mg b.i.d., 15% of patients experienced hand-foot syndrome of grade 2 or 3 (Eur. J. Cancer 2006;42:548–56).

As with the drug eruptions that occur with epidermal growth factor inhibitors such as cetuximab and erlotinib, the patients who experienced sorafenib hand-foot syndrome had significantly longer times to progression than did those who did not experience the skin toxicity.

Some oncologists believe that the sorafenib-associated syndrome is the same as the drug eruption known as “Ara-C syndrome,” a painful erythematous palmar/plantar eruption seen in leukemia patients receiving intravenous treatment with cytosine arabinoside (Ara-C).

Dr. Heald disagreed, though, noting that Ara-C syndrome doesn't cause the “funky split peeling” that is worse distally and improves farther up the limb, basically disappearing above the elbow or knee.

Treatment of sorafenib hand-foot syndrome depends on its severity. Topical steroids to minimize the peeling usually suffice for patients with grade 1 disease involving minimal erythema. Topical steroids should also be tried first in patients with grade 2 disease, defined as peeling, bullae, and edema that don't interfere with activities of daily living. Keratinolytic agents such as urea may be helpful in these patients as well, he said.

But for patients with grade 2 disease that is refractory to topical steroids and for those with grade 3 disease that interferes with activities of daily living, Dr. Heald recommended working with the patient's oncologist to interrupt the sorafenib therapy and restart it at a lower dose. In the published phase III trial, doses were reduced in 13% and interrupted in 21% of the sorafenib group because of adverse events, most of which were due to hand-foot skin reactions or gastrointestinal events.

As the off-label use of sorafenib increases for the treatment of a variety of cancers, physicians will be seeing increasing numbers of patients taking the drug. In addition to the hand-foot syndrome, 40% of the patients in the phase III trial experienced rash/desquamation, 27% had alopecia, and 19% had pruritus, compared with 2% or less of those adverse events in the placebo group.

Currently, investigators are looking at additional uses for sorafenib. One published phase II study involving 37 patients with advanced melanoma found little or no antitumor activity with 400 mg b.i.d. sorafenib monotherapy (Brit. J. Cancer 2006;95:581–6), and a manufacturer-funded, phase II randomized trial of sorafenib or placebo in combination with carboplatin and paclitaxel as second-line therapy in 277 patients with advanced melanoma failed to reach its primary end point of progression-free survival.

Bayer and Onyx, however, are continuing to investigate the drug's use in melanoma. An ongoing phase II study using sorafenib in combination with dacarbazine as first-line therapy has thus far shown a 50% improvement in progression-free survival, Onyx spokesperson Julie Wood said in an interview.

At the same time, at least two other externally sponsored phase II studies are also looking at combination therapy with sorafenib in treating melanoma. Other trials are investigating its use for liver, lung, and breast cancer, she said.

In any case, Dr. Heald noted, “As use of this drug spreads out from renal cell carcinoma, we'll be seeing more and more hand-foot syndrome.”

'If you haven't seen this, I can tell you it's coming to a patient near you as the use of this drug picks up.' DR. HEALD

Grade 2 hand-foot syndrome, causing peeling on the plantar surface, is shown on a man who took sorafenib for 2 months.

Grade 3 syndrome appeared as hemorrhagic, pustular acral lesions on the hands of this patient who needed a lower dose. Photos courtesy Dr. Peter W. Heald

The American Diabetes Association has issued a new consensus statement addressing the diagnosis, treatment, and prevention of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults with diabetes.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Mortality in DKA patients is less than 5% in experienced treatment centers, whereas HHS mortality remains high, at about 11%. The annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1,000 patients with diabetes, with an estimated hospital cost exceeding $1 billion a year, Dr. Abbas E. Kitabchi and his associates said (Diabetes Care 2006;29:2739–48).

Although most patients with DKA have autoimmune type 1 diabetes, patients with type 2 diabetes are also at risk during acute stress, such as that caused by trauma, surgery, or infection. Moreover, during the past decade, an increasing number of DKA cases without precipitating causes have been reported in individuals with type 2 diabetes, particularly those from minority groups.

Inadequate or inappropriate insulin therapy and infection are the two most common precipitating factors in the development of both DKA and HHS. Although HHS typically evolves over several days to weeks, the evolution of DKA in type 1 or type 2 diabetes tends to be much shorter. The classic picture of DKA includes a history of polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, weakness, mental status change, and coma. In HHS, the most common clinical presentation is altered sensorium, with signs of dehydration.

Initial laboratory evaluations of patients with suspected DKA or HHS should include the determination of plasma glucose; blood urea nitrogen; creatinine; serum ketones; electrolytes (with calculated anion gap); osmolality; urinalysis and urine ketones by dipstick; initial arterial blood gases; and complete blood count with differential. If clinically indicated, an electrocardiogram; chest x-ray; and urine, sputum, or blood cultures should also be obtained, said Dr. Kitabchi, chief of the division of endocrinology, diabetes, and metabolism at the University of Tennessee, Memphis, and associates.

Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia, they said.

Successful treatment of DKA and HHS requires the correction of dehydration, hyperglycemia, and electrolyte imbalances, as well as the identification of comorbid precipitating events and—above all—frequent patient monitoring. Protocols for the management of both DKA and HHS are included in the document, which is available free online (http://care.diabetesjournals.org

Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion. Successful progress with fluid replacement is judged by hemodynamic monitoring (improvement in blood pressure), measurement of fluid input and output, laboratory values, and clinical examination. Adequate rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy.

Unless the episode of DKA is uncomplicated and mild or moderate, regular insulin by continuous intravenous infusion is the treatment of choice. However, recent data suggest that the use of subcutaneous rapid-acting insulin analogs in the management of patients with uncomplicated DKA could allow for treatment in general wards or emergency departments, thus avoiding admission to the intensive care unit. Direct measurement of β-hydroxybutyrate (β—OHB) in the blood is the preferred method for monitoring DKA, and has become more convenient with the recent development of bedside meters capable of measuring β—OHB in whole blood, they noted.

Criteria for resolution of DKA include glucose less than 200 mg/dL, serum bicarbonate greater than or equal to 18 mEq/L, and venous pH greater than 7.3. When a patient is able to eat, a multiple-dose schedule involving a combination of basal and premeal bolus insulins should be initiated as needed to control plasma glucose. To prevent hypokalemia, potassium replacement is started after serum levels drop to less than 5.3 mEq/L, assuming the presence of adequate urine output at 50 mL/hour.

The use of bicarbonate in DKA remains controversial. At a pH greater than 7.0, the administration of insulin blocks lipolysis and resolves ketoacidosis without any added bicarbonate. However, limited data do support the use of bicarbonate—along with potassium supplementation—in patients with pH values lower than 7.0, and particularly in those with levels lower than 6.9, for whom the risk for severe acidosis is elevated.

Routine use of phosphate is not indicated in the treatment of DKA or HHS; data suggest it provides no clinical benefit. However, careful phosphate replacement may be indicated in some patients with cardiac dysfunction, anemia, or respiratory depression in order to minimize the risks associated with hypophosphatemia.

Studies cited in the guideline were supported by grants from the U.S. Public Health Service, National Institutes of Health, Novo-Nordisk Inc., Eli Lilly & Co., American Diabetes Association, and Abe Goodman Fund.

The American Diabetes Association has issued a new consensus statement addressing the diagnosis, treatment, and prevention of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults with diabetes.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Mortality in DKA patients is less than 5% in experienced treatment centers, whereas HHS mortality remains high, at about 11%. The annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1,000 patients with diabetes, with an estimated hospital cost exceeding $1 billion a year, Dr. Abbas E. Kitabchi and his associates said (Diabetes Care 2006;29:2739–48).

Although most patients with DKA have autoimmune type 1 diabetes, patients with type 2 diabetes are also at risk during acute stress, such as that caused by trauma, surgery, or infection. Moreover, during the past decade, an increasing number of DKA cases without precipitating causes have been reported in individuals with type 2 diabetes, particularly those from minority groups.

Inadequate or inappropriate insulin therapy and infection are the two most common precipitating factors in the development of both DKA and HHS. Although HHS typically evolves over several days to weeks, the evolution of DKA in type 1 or type 2 diabetes tends to be much shorter. The classic picture of DKA includes a history of polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, weakness, mental status change, and coma. In HHS, the most common clinical presentation is altered sensorium, with signs of dehydration.

Initial laboratory evaluations of patients with suspected DKA or HHS should include the determination of plasma glucose; blood urea nitrogen; creatinine; serum ketones; electrolytes (with calculated anion gap); osmolality; urinalysis and urine ketones by dipstick; initial arterial blood gases; and complete blood count with differential. If clinically indicated, an electrocardiogram; chest x-ray; and urine, sputum, or blood cultures should also be obtained, said Dr. Kitabchi, chief of the division of endocrinology, diabetes, and metabolism at the University of Tennessee, Memphis, and associates.

Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia, they said.

Successful treatment of DKA and HHS requires the correction of dehydration, hyperglycemia, and electrolyte imbalances, as well as the identification of comorbid precipitating events and—above all—frequent patient monitoring. Protocols for the management of both DKA and HHS are included in the document, which is available free online (http://care.diabetesjournals.org

Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion. Successful progress with fluid replacement is judged by hemodynamic monitoring (improvement in blood pressure), measurement of fluid input and output, laboratory values, and clinical examination. Adequate rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy.

Unless the episode of DKA is uncomplicated and mild or moderate, regular insulin by continuous intravenous infusion is the treatment of choice. However, recent data suggest that the use of subcutaneous rapid-acting insulin analogs in the management of patients with uncomplicated DKA could allow for treatment in general wards or emergency departments, thus avoiding admission to the intensive care unit. Direct measurement of β-hydroxybutyrate (β—OHB) in the blood is the preferred method for monitoring DKA, and has become more convenient with the recent development of bedside meters capable of measuring β—OHB in whole blood, they noted.

Criteria for resolution of DKA include glucose less than 200 mg/dL, serum bicarbonate greater than or equal to 18 mEq/L, and venous pH greater than 7.3. When a patient is able to eat, a multiple-dose schedule involving a combination of basal and premeal bolus insulins should be initiated as needed to control plasma glucose. To prevent hypokalemia, potassium replacement is started after serum levels drop to less than 5.3 mEq/L, assuming the presence of adequate urine output at 50 mL/hour.

The use of bicarbonate in DKA remains controversial. At a pH greater than 7.0, the administration of insulin blocks lipolysis and resolves ketoacidosis without any added bicarbonate. However, limited data do support the use of bicarbonate—along with potassium supplementation—in patients with pH values lower than 7.0, and particularly in those with levels lower than 6.9, for whom the risk for severe acidosis is elevated.

Routine use of phosphate is not indicated in the treatment of DKA or HHS; data suggest it provides no clinical benefit. However, careful phosphate replacement may be indicated in some patients with cardiac dysfunction, anemia, or respiratory depression in order to minimize the risks associated with hypophosphatemia.

Studies cited in the guideline were supported by grants from the U.S. Public Health Service, National Institutes of Health, Novo-Nordisk Inc., Eli Lilly & Co., American Diabetes Association, and Abe Goodman Fund.

The American Diabetes Association has issued a new consensus statement addressing the diagnosis, treatment, and prevention of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults with diabetes.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Mortality in DKA patients is less than 5% in experienced treatment centers, whereas HHS mortality remains high, at about 11%. The annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1,000 patients with diabetes, with an estimated hospital cost exceeding $1 billion a year, Dr. Abbas E. Kitabchi and his associates said (Diabetes Care 2006;29:2739–48).

Although most patients with DKA have autoimmune type 1 diabetes, patients with type 2 diabetes are also at risk during acute stress, such as that caused by trauma, surgery, or infection. Moreover, during the past decade, an increasing number of DKA cases without precipitating causes have been reported in individuals with type 2 diabetes, particularly those from minority groups.

Inadequate or inappropriate insulin therapy and infection are the two most common precipitating factors in the development of both DKA and HHS. Although HHS typically evolves over several days to weeks, the evolution of DKA in type 1 or type 2 diabetes tends to be much shorter. The classic picture of DKA includes a history of polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, weakness, mental status change, and coma. In HHS, the most common clinical presentation is altered sensorium, with signs of dehydration.

Initial laboratory evaluations of patients with suspected DKA or HHS should include the determination of plasma glucose; blood urea nitrogen; creatinine; serum ketones; electrolytes (with calculated anion gap); osmolality; urinalysis and urine ketones by dipstick; initial arterial blood gases; and complete blood count with differential. If clinically indicated, an electrocardiogram; chest x-ray; and urine, sputum, or blood cultures should also be obtained, said Dr. Kitabchi, chief of the division of endocrinology, diabetes, and metabolism at the University of Tennessee, Memphis, and associates.

Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia, they said.

Successful treatment of DKA and HHS requires the correction of dehydration, hyperglycemia, and electrolyte imbalances, as well as the identification of comorbid precipitating events and—above all—frequent patient monitoring. Protocols for the management of both DKA and HHS are included in the document, which is available free online (http://care.diabetesjournals.org

Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion. Successful progress with fluid replacement is judged by hemodynamic monitoring (improvement in blood pressure), measurement of fluid input and output, laboratory values, and clinical examination. Adequate rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy.

Unless the episode of DKA is uncomplicated and mild or moderate, regular insulin by continuous intravenous infusion is the treatment of choice. However, recent data suggest that the use of subcutaneous rapid-acting insulin analogs in the management of patients with uncomplicated DKA could allow for treatment in general wards or emergency departments, thus avoiding admission to the intensive care unit. Direct measurement of β-hydroxybutyrate (β—OHB) in the blood is the preferred method for monitoring DKA, and has become more convenient with the recent development of bedside meters capable of measuring β—OHB in whole blood, they noted.

Criteria for resolution of DKA include glucose less than 200 mg/dL, serum bicarbonate greater than or equal to 18 mEq/L, and venous pH greater than 7.3. When a patient is able to eat, a multiple-dose schedule involving a combination of basal and premeal bolus insulins should be initiated as needed to control plasma glucose. To prevent hypokalemia, potassium replacement is started after serum levels drop to less than 5.3 mEq/L, assuming the presence of adequate urine output at 50 mL/hour.

The use of bicarbonate in DKA remains controversial. At a pH greater than 7.0, the administration of insulin blocks lipolysis and resolves ketoacidosis without any added bicarbonate. However, limited data do support the use of bicarbonate—along with potassium supplementation—in patients with pH values lower than 7.0, and particularly in those with levels lower than 6.9, for whom the risk for severe acidosis is elevated.

Routine use of phosphate is not indicated in the treatment of DKA or HHS; data suggest it provides no clinical benefit. However, careful phosphate replacement may be indicated in some patients with cardiac dysfunction, anemia, or respiratory depression in order to minimize the risks associated with hypophosphatemia.

Studies cited in the guideline were supported by grants from the U.S. Public Health Service, National Institutes of Health, Novo-Nordisk Inc., Eli Lilly & Co., American Diabetes Association, and Abe Goodman Fund.

BETHESDA, MD. — The first combination vaccine to protect against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b was deemed safe and effective by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee vaccines advisory panel.

The panel voted unanimously to support the safety of Sanofi-Pasteur's Pentacel, which has been licensed in Canada since 1997 and used exclusively there since 1998, with over 12 million doses distributed. It also is used in several European countries.

All 15 of the panel's permanent and temporary voting members also endorsed the efficacy of the vaccine's diphtheria, tetanus, and polio components. However, a few panelists expressed concern about its protection against pertussis and Hib, based on conflicting study findings regarding noninferiority of Pentacel compared with currently licensed vaccines or their equivalents.

But even the members who voiced those concerns still generally supported the vaccine's licensure, with the caveat that ongoing disease surveillance continues and that extra efforts are made to monitor Hib rates in high-risk populations.

“For the [Hib] component, I don't feel I have adequate data,” said biostatistician Steven Self, Ph.D. But, he later stated, “On balance, yes, the vaccine has public health benefit.”

Indeed, several panel members noted that a small diminution in immunogenicity of one vaccine component might well be counterbalanced by improved overall vaccine coverage rates resulting from the reduction in injections.

Compared with giving DTaP, IPV, and Hib separately, use of Pentacel in children at 2, 4, 6, and 15–18 months of age would reduce the total required number of shots in infants and toddlers by seven, said Dr. David Greenberg, Sanofi-Pasteur's director of scientific and medical affairs.

Panel member Dr. John Modlin, professor of pediatrics at Dartmouth-Hitchcock Medical Center, pointed out another potential advantage to Pentacel: It would avoid the “conundrum” regarding hepatitis B vaccine, which is included in the currently licensed combination vaccines Comvax (Hib and hepatitis B) and Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio).

Since those combinations can't be given prior to 2 months of age, infants who receive their first dose of hepatitis B vaccine at birth end up with an extra dose of hepatitis B vaccine by the time they finish the primary series. Although this is not a safety issue, it is a cost issue in some settings and has been cited as a disincentive to giving the first hepatitis B dose at birth, a practice that has been endorsed by multiple advisory bodies.

“Introducing this vaccine would add versatility, especially with regard to hepatitis B. If you want to give the birth dose, it simplifies the schedule,” Dr. Modlin, former chair of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, said in an interview.

Sanofi-Pasteur's U.S. licensure application was based on data from five clinical studies involving a total of 7,146 Pentacel recipients. Safety and immunogenicity were examined in four studies, and one additional study examined immunogenicity compared with the company's currently licensed Daptacel (DTaP) vaccine. Two of the studies examined the concomitant use of Pentacel with Prevnar for the infant series, and with Prevnar, measles-mumps-rubella, and varicella vaccines at 15–18 months of age.

Safety data, presented by Dr. Luc Kuykens, Sanofi-Pasteur's vice president for regulatory affairs, showed no unexpected adverse events, with rates of local and systemic reactions comparable to those seen with currently licensed vaccines. Postmarketing data in Canada also support the safety of Pentacel, he said.

The FDA's safety review of Pentacel, presented by Dr. Karen Farizo, also did not detect any unexpected problems.

However, FDA reviewer Theresa Finn, Ph.D., did identify two “concerns” with regard to Pentacel's immunogenicity, noting that the criteria for “noninferiority” were not met for the Hib and pertussis components in some of the studies.

The immunogenicity data from the five studies had been presented in detail by Dr. Michael Decker, Sanofi-Pasteur's vice president of scientific and medical affairs.

In response to Dr. Finn's analysis of the pertussis data, Dr. Decker noted that a pertussis vaccine's ability to produce immune responses to individual pertussis antigens has been shown not to correlate with degree of protection, and that Pentacel's overall protection against pertussis is comparable to currently used vaccines.

As for Hib, only one of two studies had not demonstrated noninferiority; the other one had. Moreover, the comparator in the former study was not a U.S.-licensed product, he explained.

The advisory panel was further reassured by epidemiologic data from Canada, presented by Dr. Scott Halperin, professor of pediatrics at Dalhousie University, Halifax, N.S. Multiple surveillance systems in that country confirm very low rates of pertussis and Hib disease in infants and children, he said.

In an interview following the hearing, Dr. Decker noted that only about half of U.S. physicians are using the currently available combination vaccines Comvax and Pediarix for routine infant immunization, while the other 50% are still using the separate ones. “That tells you physicians are not fully happy with their choices.”

Indeed, Dr. Modlin noted, increasing competition in the combination vaccine market would be another “big advantage” of licensing Pentacel. “Competition is always a good thing, particularly with regard to public health programs.”

BETHESDA, MD. — The first combination vaccine to protect against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b was deemed safe and effective by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee vaccines advisory panel.

The panel voted unanimously to support the safety of Sanofi-Pasteur's Pentacel, which has been licensed in Canada since 1997 and used exclusively there since 1998, with over 12 million doses distributed. It also is used in several European countries.

All 15 of the panel's permanent and temporary voting members also endorsed the efficacy of the vaccine's diphtheria, tetanus, and polio components. However, a few panelists expressed concern about its protection against pertussis and Hib, based on conflicting study findings regarding noninferiority of Pentacel compared with currently licensed vaccines or their equivalents.

But even the members who voiced those concerns still generally supported the vaccine's licensure, with the caveat that ongoing disease surveillance continues and that extra efforts are made to monitor Hib rates in high-risk populations.

“For the [Hib] component, I don't feel I have adequate data,” said biostatistician Steven Self, Ph.D. But, he later stated, “On balance, yes, the vaccine has public health benefit.”

Indeed, several panel members noted that a small diminution in immunogenicity of one vaccine component might well be counterbalanced by improved overall vaccine coverage rates resulting from the reduction in injections.

Compared with giving DTaP, IPV, and Hib separately, use of Pentacel in children at 2, 4, 6, and 15–18 months of age would reduce the total required number of shots in infants and toddlers by seven, said Dr. David Greenberg, Sanofi-Pasteur's director of scientific and medical affairs.

Panel member Dr. John Modlin, professor of pediatrics at Dartmouth-Hitchcock Medical Center, pointed out another potential advantage to Pentacel: It would avoid the “conundrum” regarding hepatitis B vaccine, which is included in the currently licensed combination vaccines Comvax (Hib and hepatitis B) and Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio).

Since those combinations can't be given prior to 2 months of age, infants who receive their first dose of hepatitis B vaccine at birth end up with an extra dose of hepatitis B vaccine by the time they finish the primary series. Although this is not a safety issue, it is a cost issue in some settings and has been cited as a disincentive to giving the first hepatitis B dose at birth, a practice that has been endorsed by multiple advisory bodies.

“Introducing this vaccine would add versatility, especially with regard to hepatitis B. If you want to give the birth dose, it simplifies the schedule,” Dr. Modlin, former chair of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, said in an interview.

Sanofi-Pasteur's U.S. licensure application was based on data from five clinical studies involving a total of 7,146 Pentacel recipients. Safety and immunogenicity were examined in four studies, and one additional study examined immunogenicity compared with the company's currently licensed Daptacel (DTaP) vaccine. Two of the studies examined the concomitant use of Pentacel with Prevnar for the infant series, and with Prevnar, measles-mumps-rubella, and varicella vaccines at 15–18 months of age.

Safety data, presented by Dr. Luc Kuykens, Sanofi-Pasteur's vice president for regulatory affairs, showed no unexpected adverse events, with rates of local and systemic reactions comparable to those seen with currently licensed vaccines. Postmarketing data in Canada also support the safety of Pentacel, he said.

The FDA's safety review of Pentacel, presented by Dr. Karen Farizo, also did not detect any unexpected problems.

However, FDA reviewer Theresa Finn, Ph.D., did identify two “concerns” with regard to Pentacel's immunogenicity, noting that the criteria for “noninferiority” were not met for the Hib and pertussis components in some of the studies.

The immunogenicity data from the five studies had been presented in detail by Dr. Michael Decker, Sanofi-Pasteur's vice president of scientific and medical affairs.

In response to Dr. Finn's analysis of the pertussis data, Dr. Decker noted that a pertussis vaccine's ability to produce immune responses to individual pertussis antigens has been shown not to correlate with degree of protection, and that Pentacel's overall protection against pertussis is comparable to currently used vaccines.

As for Hib, only one of two studies had not demonstrated noninferiority; the other one had. Moreover, the comparator in the former study was not a U.S.-licensed product, he explained.

The advisory panel was further reassured by epidemiologic data from Canada, presented by Dr. Scott Halperin, professor of pediatrics at Dalhousie University, Halifax, N.S. Multiple surveillance systems in that country confirm very low rates of pertussis and Hib disease in infants and children, he said.

In an interview following the hearing, Dr. Decker noted that only about half of U.S. physicians are using the currently available combination vaccines Comvax and Pediarix for routine infant immunization, while the other 50% are still using the separate ones. “That tells you physicians are not fully happy with their choices.”

Indeed, Dr. Modlin noted, increasing competition in the combination vaccine market would be another “big advantage” of licensing Pentacel. “Competition is always a good thing, particularly with regard to public health programs.”

BETHESDA, MD. — The first combination vaccine to protect against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b was deemed safe and effective by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee vaccines advisory panel.

The panel voted unanimously to support the safety of Sanofi-Pasteur's Pentacel, which has been licensed in Canada since 1997 and used exclusively there since 1998, with over 12 million doses distributed. It also is used in several European countries.

All 15 of the panel's permanent and temporary voting members also endorsed the efficacy of the vaccine's diphtheria, tetanus, and polio components. However, a few panelists expressed concern about its protection against pertussis and Hib, based on conflicting study findings regarding noninferiority of Pentacel compared with currently licensed vaccines or their equivalents.

But even the members who voiced those concerns still generally supported the vaccine's licensure, with the caveat that ongoing disease surveillance continues and that extra efforts are made to monitor Hib rates in high-risk populations.

“For the [Hib] component, I don't feel I have adequate data,” said biostatistician Steven Self, Ph.D. But, he later stated, “On balance, yes, the vaccine has public health benefit.”

Indeed, several panel members noted that a small diminution in immunogenicity of one vaccine component might well be counterbalanced by improved overall vaccine coverage rates resulting from the reduction in injections.

Compared with giving DTaP, IPV, and Hib separately, use of Pentacel in children at 2, 4, 6, and 15–18 months of age would reduce the total required number of shots in infants and toddlers by seven, said Dr. David Greenberg, Sanofi-Pasteur's director of scientific and medical affairs.

Panel member Dr. John Modlin, professor of pediatrics at Dartmouth-Hitchcock Medical Center, pointed out another potential advantage to Pentacel: It would avoid the “conundrum” regarding hepatitis B vaccine, which is included in the currently licensed combination vaccines Comvax (Hib and hepatitis B) and Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio).

Since those combinations can't be given prior to 2 months of age, infants who receive their first dose of hepatitis B vaccine at birth end up with an extra dose of hepatitis B vaccine by the time they finish the primary series. Although this is not a safety issue, it is a cost issue in some settings and has been cited as a disincentive to giving the first hepatitis B dose at birth, a practice that has been endorsed by multiple advisory bodies.

“Introducing this vaccine would add versatility, especially with regard to hepatitis B. If you want to give the birth dose, it simplifies the schedule,” Dr. Modlin, former chair of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, said in an interview.

Sanofi-Pasteur's U.S. licensure application was based on data from five clinical studies involving a total of 7,146 Pentacel recipients. Safety and immunogenicity were examined in four studies, and one additional study examined immunogenicity compared with the company's currently licensed Daptacel (DTaP) vaccine. Two of the studies examined the concomitant use of Pentacel with Prevnar for the infant series, and with Prevnar, measles-mumps-rubella, and varicella vaccines at 15–18 months of age.

Safety data, presented by Dr. Luc Kuykens, Sanofi-Pasteur's vice president for regulatory affairs, showed no unexpected adverse events, with rates of local and systemic reactions comparable to those seen with currently licensed vaccines. Postmarketing data in Canada also support the safety of Pentacel, he said.

The FDA's safety review of Pentacel, presented by Dr. Karen Farizo, also did not detect any unexpected problems.

However, FDA reviewer Theresa Finn, Ph.D., did identify two “concerns” with regard to Pentacel's immunogenicity, noting that the criteria for “noninferiority” were not met for the Hib and pertussis components in some of the studies.

The immunogenicity data from the five studies had been presented in detail by Dr. Michael Decker, Sanofi-Pasteur's vice president of scientific and medical affairs.

In response to Dr. Finn's analysis of the pertussis data, Dr. Decker noted that a pertussis vaccine's ability to produce immune responses to individual pertussis antigens has been shown not to correlate with degree of protection, and that Pentacel's overall protection against pertussis is comparable to currently used vaccines.

As for Hib, only one of two studies had not demonstrated noninferiority; the other one had. Moreover, the comparator in the former study was not a U.S.-licensed product, he explained.

The advisory panel was further reassured by epidemiologic data from Canada, presented by Dr. Scott Halperin, professor of pediatrics at Dalhousie University, Halifax, N.S. Multiple surveillance systems in that country confirm very low rates of pertussis and Hib disease in infants and children, he said.

In an interview following the hearing, Dr. Decker noted that only about half of U.S. physicians are using the currently available combination vaccines Comvax and Pediarix for routine infant immunization, while the other 50% are still using the separate ones. “That tells you physicians are not fully happy with their choices.”

Indeed, Dr. Modlin noted, increasing competition in the combination vaccine market would be another “big advantage” of licensing Pentacel. “Competition is always a good thing, particularly with regard to public health programs.”

COPENHAGEN—Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved by the U.S. Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it daily at home (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean BMI of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls. That difference was not significant.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been instructed to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, the duration of each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes, and patients spent a mean of 40.4 minutes per week in slow breathing.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

COPENHAGEN—Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved by the U.S. Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it daily at home (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean BMI of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls. That difference was not significant.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been instructed to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, the duration of each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes, and patients spent a mean of 40.4 minutes per week in slow breathing.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

COPENHAGEN—Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved by the U.S. Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it daily at home (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean BMI of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls. That difference was not significant.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been instructed to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, the duration of each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes, and patients spent a mean of 40.4 minutes per week in slow breathing.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

WASHINGTON — Efforts to make HIV screening an integral part of primary care have created a new set of educational, reimbursement, and workforce challenges for physicians.

In response, the Society of General Internal Medicine (SGIM) is gearing up to help primary care physicians incorporate routine HIV screening into their busy practices, Dr. James M. Sosman said at a meeting on HIV diagnosis and prevention and access to care.

In September, the Centers for Disease Control and Prevention issued recommendations for routine “opt-out” HIV screening of all patients aged 13–64 years. Health care providers should initiate screening unless the prevalence of undiagnosed HIV infection in their patients has been documented to be less than 0.1%. In the absence of such prevalence data, health care providers are advised to initiate voluntary HIV screening until they establish that the diagnostic yield is less than 1/1,000 patients screened, at which point screening is no longer warranted (MMWR 2006;55:RR-14).

Prevention counseling should not be required as part of HIV screening programs, according to the CDC. Although “strongly encouraged” for individuals at high risk for HIV, counseling does not have to be linked to the testing itself, the agency said.

The CDC guidelines have sparked concern that widespread HIV screening will overburden the U.S. health care system by identifying thousands of HIV-positive individuals who will require costly counseling and treatment services. An estimated 252,000–312,000 Americans are unaware that they are HIV-positive.

In anticipation of the guidelines, the SGIM obtained a 3-year grant from the CDC to develop an educational “train the trainer” program aimed at reducing barriers to early diagnosis of HIV infection and increasing patient access to preventive services in primary care settings, Dr. Sosman said at the meeting.

Clinician educators will be recruited from medical school and residency programs, and will then “serve as regional trainers, information resources, and role models for other primary care physicians,” said Dr. Sosman, medical director of the Midwest AIDS Training and Education Center, Madison, Wis. Future training sessions and presentations will include collaborations with groups not directly linked with the SGIM, including local and state medical societies, Area Health Education Centers, and other organizations.

The first half of 2007 will be devoted to information gathering. Focus groups and surveys of SGIM members will be used to ascertain current practices and identify potential barriers to implementation of the CDC guidelines. The information will be used to develop educational materials, such as slide sets, case studies, training scripts, and provider tool kits. The sessions themselves are expected to begin around the country in the latter part of the year. They will not be limited to members of SGIM or specifically to internists, said Dr. Sosman, also with the department of general internal medicine at the University of Wisconsin, Madison.

In a separate presentation at the meeting, Dr. Harvey J. Makadon of the department of medicine at Harvard Medical School, Boston, outlined potential operational challenges to incorporation of routine HIV screening in primary care settings. An informal survey among internists at his hospital revealed “a general sense that routine testing will improve current practices,” but respondents had many questions and concerns, particularly with regard to reimbursement for counseling and the process of counseling itself.

“A lot of doctors have something that they usually say [when counseling patients], and there have been articles written on the topic, but there's no formal curriculum. We're not really taught what to talk about with patients regarding HIV prevention,” Dr. Makadon remarked. “What are the best practices?”

There may be potential legal problems as well. In many states, existing laws regarding informed consent for HIV screening appear to conflict with the CDC “opt-out” guidelines, and these laws would likely need to be amended in order for the guidelines to be implemented. Until that happens, the laws supersede public health guidelines, Dr. Sosman noted.

And then there's the question of what to do with patients identified as HIV-positive, particularly those who are still healthy and asymptomatic. The number of HIV specialists in the country has remained static since the epidemic began 20 years ago, according to another speaker at the conference, Dr. M. Keith Rawlings.

“Where will the newly diagnosed patients get their medical care? I don't foresee the ability of most practitioners to absorb 25%–50% more [HIV-positive] individuals. Available resources in the community will have to be identified,” said Dr. Rawlings, medical director of the AIDS Arms Peabody Health Center, Dallas, speaking on behalf of the National Medical Association.

Dr. Sosman noted that a “team approach” to HIV/AIDS care could be implemented in primary care settings, similar to that currently used for patients with diabetes or for smoking cessation. “It works, but it's expensive,” he remarked.

Dr. Rawlings pointed out that the HIV-positive population is looking more and more like the patients primary care physicians see every day: As antiretroviral medications are allowing patients to live longer, the drugs are also associated with an increased risk for familiar conditions such as dyslipidemia, diabetes, and heart disease. “It's been a very long time since I've seen anybody in my office who has HIV as the only thing wrong with them.”

WASHINGTON — Efforts to make HIV screening an integral part of primary care have created a new set of educational, reimbursement, and workforce challenges for physicians.

In response, the Society of General Internal Medicine (SGIM) is gearing up to help primary care physicians incorporate routine HIV screening into their busy practices, Dr. James M. Sosman said at a meeting on HIV diagnosis and prevention and access to care.

In September, the Centers for Disease Control and Prevention issued recommendations for routine “opt-out” HIV screening of all patients aged 13–64 years. Health care providers should initiate screening unless the prevalence of undiagnosed HIV infection in their patients has been documented to be less than 0.1%. In the absence of such prevalence data, health care providers are advised to initiate voluntary HIV screening until they establish that the diagnostic yield is less than 1/1,000 patients screened, at which point screening is no longer warranted (MMWR 2006;55:RR-14).

Prevention counseling should not be required as part of HIV screening programs, according to the CDC. Although “strongly encouraged” for individuals at high risk for HIV, counseling does not have to be linked to the testing itself, the agency said.

The CDC guidelines have sparked concern that widespread HIV screening will overburden the U.S. health care system by identifying thousands of HIV-positive individuals who will require costly counseling and treatment services. An estimated 252,000–312,000 Americans are unaware that they are HIV-positive.

In anticipation of the guidelines, the SGIM obtained a 3-year grant from the CDC to develop an educational “train the trainer” program aimed at reducing barriers to early diagnosis of HIV infection and increasing patient access to preventive services in primary care settings, Dr. Sosman said at the meeting.

Clinician educators will be recruited from medical school and residency programs, and will then “serve as regional trainers, information resources, and role models for other primary care physicians,” said Dr. Sosman, medical director of the Midwest AIDS Training and Education Center, Madison, Wis. Future training sessions and presentations will include collaborations with groups not directly linked with the SGIM, including local and state medical societies, Area Health Education Centers, and other organizations.

The first half of 2007 will be devoted to information gathering. Focus groups and surveys of SGIM members will be used to ascertain current practices and identify potential barriers to implementation of the CDC guidelines. The information will be used to develop educational materials, such as slide sets, case studies, training scripts, and provider tool kits. The sessions themselves are expected to begin around the country in the latter part of the year. They will not be limited to members of SGIM or specifically to internists, said Dr. Sosman, also with the department of general internal medicine at the University of Wisconsin, Madison.

In a separate presentation at the meeting, Dr. Harvey J. Makadon of the department of medicine at Harvard Medical School, Boston, outlined potential operational challenges to incorporation of routine HIV screening in primary care settings. An informal survey among internists at his hospital revealed “a general sense that routine testing will improve current practices,” but respondents had many questions and concerns, particularly with regard to reimbursement for counseling and the process of counseling itself.

“A lot of doctors have something that they usually say [when counseling patients], and there have been articles written on the topic, but there's no formal curriculum. We're not really taught what to talk about with patients regarding HIV prevention,” Dr. Makadon remarked. “What are the best practices?”

There may be potential legal problems as well. In many states, existing laws regarding informed consent for HIV screening appear to conflict with the CDC “opt-out” guidelines, and these laws would likely need to be amended in order for the guidelines to be implemented. Until that happens, the laws supersede public health guidelines, Dr. Sosman noted.

And then there's the question of what to do with patients identified as HIV-positive, particularly those who are still healthy and asymptomatic. The number of HIV specialists in the country has remained static since the epidemic began 20 years ago, according to another speaker at the conference, Dr. M. Keith Rawlings.

“Where will the newly diagnosed patients get their medical care? I don't foresee the ability of most practitioners to absorb 25%–50% more [HIV-positive] individuals. Available resources in the community will have to be identified,” said Dr. Rawlings, medical director of the AIDS Arms Peabody Health Center, Dallas, speaking on behalf of the National Medical Association.

Dr. Sosman noted that a “team approach” to HIV/AIDS care could be implemented in primary care settings, similar to that currently used for patients with diabetes or for smoking cessation. “It works, but it's expensive,” he remarked.

Dr. Rawlings pointed out that the HIV-positive population is looking more and more like the patients primary care physicians see every day: As antiretroviral medications are allowing patients to live longer, the drugs are also associated with an increased risk for familiar conditions such as dyslipidemia, diabetes, and heart disease. “It's been a very long time since I've seen anybody in my office who has HIV as the only thing wrong with them.”

WASHINGTON — Efforts to make HIV screening an integral part of primary care have created a new set of educational, reimbursement, and workforce challenges for physicians.

In response, the Society of General Internal Medicine (SGIM) is gearing up to help primary care physicians incorporate routine HIV screening into their busy practices, Dr. James M. Sosman said at a meeting on HIV diagnosis and prevention and access to care.

In September, the Centers for Disease Control and Prevention issued recommendations for routine “opt-out” HIV screening of all patients aged 13–64 years. Health care providers should initiate screening unless the prevalence of undiagnosed HIV infection in their patients has been documented to be less than 0.1%. In the absence of such prevalence data, health care providers are advised to initiate voluntary HIV screening until they establish that the diagnostic yield is less than 1/1,000 patients screened, at which point screening is no longer warranted (MMWR 2006;55:RR-14).

Prevention counseling should not be required as part of HIV screening programs, according to the CDC. Although “strongly encouraged” for individuals at high risk for HIV, counseling does not have to be linked to the testing itself, the agency said.

The CDC guidelines have sparked concern that widespread HIV screening will overburden the U.S. health care system by identifying thousands of HIV-positive individuals who will require costly counseling and treatment services. An estimated 252,000–312,000 Americans are unaware that they are HIV-positive.

In anticipation of the guidelines, the SGIM obtained a 3-year grant from the CDC to develop an educational “train the trainer” program aimed at reducing barriers to early diagnosis of HIV infection and increasing patient access to preventive services in primary care settings, Dr. Sosman said at the meeting.

Clinician educators will be recruited from medical school and residency programs, and will then “serve as regional trainers, information resources, and role models for other primary care physicians,” said Dr. Sosman, medical director of the Midwest AIDS Training and Education Center, Madison, Wis. Future training sessions and presentations will include collaborations with groups not directly linked with the SGIM, including local and state medical societies, Area Health Education Centers, and other organizations.

The first half of 2007 will be devoted to information gathering. Focus groups and surveys of SGIM members will be used to ascertain current practices and identify potential barriers to implementation of the CDC guidelines. The information will be used to develop educational materials, such as slide sets, case studies, training scripts, and provider tool kits. The sessions themselves are expected to begin around the country in the latter part of the year. They will not be limited to members of SGIM or specifically to internists, said Dr. Sosman, also with the department of general internal medicine at the University of Wisconsin, Madison.

In a separate presentation at the meeting, Dr. Harvey J. Makadon of the department of medicine at Harvard Medical School, Boston, outlined potential operational challenges to incorporation of routine HIV screening in primary care settings. An informal survey among internists at his hospital revealed “a general sense that routine testing will improve current practices,” but respondents had many questions and concerns, particularly with regard to reimbursement for counseling and the process of counseling itself.

“A lot of doctors have something that they usually say [when counseling patients], and there have been articles written on the topic, but there's no formal curriculum. We're not really taught what to talk about with patients regarding HIV prevention,” Dr. Makadon remarked. “What are the best practices?”

There may be potential legal problems as well. In many states, existing laws regarding informed consent for HIV screening appear to conflict with the CDC “opt-out” guidelines, and these laws would likely need to be amended in order for the guidelines to be implemented. Until that happens, the laws supersede public health guidelines, Dr. Sosman noted.

And then there's the question of what to do with patients identified as HIV-positive, particularly those who are still healthy and asymptomatic. The number of HIV specialists in the country has remained static since the epidemic began 20 years ago, according to another speaker at the conference, Dr. M. Keith Rawlings.

“Where will the newly diagnosed patients get their medical care? I don't foresee the ability of most practitioners to absorb 25%–50% more [HIV-positive] individuals. Available resources in the community will have to be identified,” said Dr. Rawlings, medical director of the AIDS Arms Peabody Health Center, Dallas, speaking on behalf of the National Medical Association.

Dr. Sosman noted that a “team approach” to HIV/AIDS care could be implemented in primary care settings, similar to that currently used for patients with diabetes or for smoking cessation. “It works, but it's expensive,” he remarked.

Dr. Rawlings pointed out that the HIV-positive population is looking more and more like the patients primary care physicians see every day: As antiretroviral medications are allowing patients to live longer, the drugs are also associated with an increased risk for familiar conditions such as dyslipidemia, diabetes, and heart disease. “It's been a very long time since I've seen anybody in my office who has HIV as the only thing wrong with them.”

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

Last year, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]). Kaiser Permanente, which is the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“We have the capacity to do it, and we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the entire U.S. population, including more than 16,000 active HIV-infected patients. The numbers vary widely by region, from about 180 patients in Ohio to nearly 5,500 in California.

Currently, nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. However, more than 90% of patients who are diagnosed enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other potential barriers to expanded HIV screening in managed care include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening.

Although most managed care organizations do support targeted screening for pregnant women and for individuals with high-risk behavior, they have not yet generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states that Kaiser now serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, pre- and posttest counseling, and patient education.

“Testing in [Kaiser] is the desired norm. … We are uncomfortable screening without a proper testing process,” explained Dr. Horberg.

However, he added, despite the potential roadblocks, “We are confident that we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Because the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability. And that number includes about 100,000 who have already been diagnosed with HIV/AIDS, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis that was done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of their diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care. This service is “optional” and thus depends on the individual state's policy.

A recent study by researchers at George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling, with 19 of those also covering prenatal and perinatal counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done.

There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain,” the definition states.

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes that the federal government will need to contribute more to Medicaid for the CDC guidelines to be fully implemented.

“It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments is going to be adequate to implement population-based HIV screening. Medicaid, with its significant reach into low-income populations and ethnic and racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs,” Ms. Lubinski noted.

'We have the capacity to do [routine, universal HIV screening], and we have the will to do it. But it is a lot of money.' DR. HORBERG

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

Last year, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]). Kaiser Permanente, which is the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“We have the capacity to do it, and we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the entire U.S. population, including more than 16,000 active HIV-infected patients. The numbers vary widely by region, from about 180 patients in Ohio to nearly 5,500 in California.

Currently, nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. However, more than 90% of patients who are diagnosed enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other potential barriers to expanded HIV screening in managed care include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening.

Although most managed care organizations do support targeted screening for pregnant women and for individuals with high-risk behavior, they have not yet generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states that Kaiser now serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, pre- and posttest counseling, and patient education.

“Testing in [Kaiser] is the desired norm. … We are uncomfortable screening without a proper testing process,” explained Dr. Horberg.

However, he added, despite the potential roadblocks, “We are confident that we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Because the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability. And that number includes about 100,000 who have already been diagnosed with HIV/AIDS, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis that was done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of their diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care. This service is “optional” and thus depends on the individual state's policy.

A recent study by researchers at George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling, with 19 of those also covering prenatal and perinatal counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done.

There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain,” the definition states.

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes that the federal government will need to contribute more to Medicaid for the CDC guidelines to be fully implemented.

“It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments is going to be adequate to implement population-based HIV screening. Medicaid, with its significant reach into low-income populations and ethnic and racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs,” Ms. Lubinski noted.

'We have the capacity to do [routine, universal HIV screening], and we have the will to do it. But it is a lot of money.' DR. HORBERG

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

Last year, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]). Kaiser Permanente, which is the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“We have the capacity to do it, and we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the entire U.S. population, including more than 16,000 active HIV-infected patients. The numbers vary widely by region, from about 180 patients in Ohio to nearly 5,500 in California.

Currently, nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. However, more than 90% of patients who are diagnosed enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other potential barriers to expanded HIV screening in managed care include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening.

Although most managed care organizations do support targeted screening for pregnant women and for individuals with high-risk behavior, they have not yet generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states that Kaiser now serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, pre- and posttest counseling, and patient education.

“Testing in [Kaiser] is the desired norm. … We are uncomfortable screening without a proper testing process,” explained Dr. Horberg.

However, he added, despite the potential roadblocks, “We are confident that we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Because the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability. And that number includes about 100,000 who have already been diagnosed with HIV/AIDS, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis that was done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of their diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care. This service is “optional” and thus depends on the individual state's policy.

A recent study by researchers at George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling, with 19 of those also covering prenatal and perinatal counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done.

There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain,” the definition states.

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes that the federal government will need to contribute more to Medicaid for the CDC guidelines to be fully implemented.

“It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments is going to be adequate to implement population-based HIV screening. Medicaid, with its significant reach into low-income populations and ethnic and racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs,” Ms. Lubinski noted.

'We have the capacity to do [routine, universal HIV screening], and we have the will to do it. But it is a lot of money.' DR. HORBERG

The days of hemoglobin A_1c reporting may be numbered.

If the final results of the 11-center International HbA_1c/Mean Blood Glucose (MBG) Study demonstrate that hemoglobin A_1c levels can be mathematically correlated with equivalent mean blood glucose levels in all diabetic populations, a decision could be made as early as 2008 for laboratories to drop A_1c entirely and simply report patients' mean blood glucose instead.

For many in the diabetes community, the move would be a positive one. “People can relate to average blood glucose. The term hemoglobin A_1c is extremely confusing,” said Richard Kahn, Ph.D., chief scientific officer of the American Diabetes Association (ADA).

But any decision to change the way glycemia is reported will be made very carefully, with full awareness of the potentially enormous impact on physicians and patients, according to Dr. David B. Sacks, a pathologist at Brigham and Women's Hospital and Harvard Medical School, Boston, who has been involved in the process from the laboratory medicine side. “We don't want to scare people. Nothing will be changed without people being notified and given lots of preparation time.”

Preliminary study data suggest a correlation tight enough to provide an equation to translate HbA_1c values to equivalent mean blood glucose, Dr. Robert J. Heine, director of the Diabetes Center at Vrije University, Amsterdam, reported in December at the International Diabetes Federation (IDF) meeting in Cape Town, South Africa. Interim data will be presented at the American Diabetes Association's annual Scientific Sessions in June 2007 in Chicago, and final results will be announced at the annual meeting of the European Association for the Study of Diabetes (EASD), to be held in Amsterdam in September 2007.

The study was prompted by the recent adoption of a new reference method for the measurement of hemoglobin A_1c in human blood by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Whereas previous assays utilized only high-performance liquid chromatography (HPLC) to separate glycated from nonglycated hemoglobin, the new method adds a second step involving mass spectroscopy, which further filters out various glycated peptides that are not actually A_1c (Clin. Chem. Lab. Med. 2002;40:78–89).

The result, a more “pure” measure of HbA_1c, is about 1.3%–1.9% lower: A 7% with the old reference method, for example, is 5.3% with the new IFCC method, Dr. Sacks said.

Realizing that a switch to reporting the new numbers would likely generate mass confusion, the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation convened a 14-member working group in 2004 to determine how to proceed. Early on, they agreed unanimously that the same HbA_1c values should be reported globally and that laboratory instrument manufacturers should not make any changes to the current method of A_1c reporting until sufficient data could be collected to link HbA_1c with mean blood glucose. Planning for the International HbA_1c/MBG Study subsequently began in January 2005.

The new two-step IFCC reference method has been in place for about a year. It is not used with actual patient samples because of cost and time constraints. Rather, manufacturers use the values generated by it to calibrate their laboratory A_1c assays, which for the time being are still programmed to report the familiar A_1c numbers. But those settings could be changed, depending on what the working group decides.

Among the options the working group will consider, switching to mean blood glucose reporting alone appears to be the most likely if the results of the International HbA_1c/MBG Study are definitive. A collaboration of the ADA and the EASD, the study is “supported by generous educational grants” from Minimed-Medtronic, Lifescan, Hemocue, Sanofi-Aventis, Abbott Diabetes Care, GlaxoSmithKline, Bayer, and Merck & Co. It involves 300 patients each with type 1 and type 2 diabetes and 100 nondiabetic subjects from six U.S. cities, the Netherlands, Italy, Denmark, India, and Cameroon.

Glycemia is measured by a continuous glucose monitoring system (CGMS) for 2 days every month for 4 months, along with an eight-point self-monitoring daily profile during the CGMS days. Subjects also perform self-monitoring of blood glucose four times daily for a minimum of 3 days a week. Hemoglobin A_1c is measured every month for 4 months.

The aim is to establish the mathematical correlation between A_1c and mean blood glucose across diabetes types, genders, and ethnicities. Although there are existing data correlating HbA_1c with mean blood glucose—and indeed, many laboratories currently report both numbers—those values were generated from old studies using only infrequent finger-stick monitoring, Dr. Heine explained at the IDF meeting.

If the mean blood glucose study does not generate adequate data—or if other factors intervene—the working group will consider other options. The simplest would be to do nothing, leaving the current A_1c values in place. While that would mean continuing to report numbers that aren't totally accurate, it would have the distinct advantage of not rocking the boat.

Moreover, the current A_1c values are directly traceable to outcomes from both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study, allowing for risk assessment for the diabetes-related complications observed in those landmark trials.

Far less likely is a decision to switch to reporting the lower IFCC numbers as percentages. Although some IFCC members had initially pushed for that, the majority have now come to realize that it would just cause too much confusion, Dr. Sacks said.

In addition, there is actually evidence to suggest that lowering the reported A_1c values might even worsen diabetes control. A study done in Sweden, where reported A_1c values were changed twice during the 1990s, showed that glucose control actually improved by about 0.5% among 49 children and adolescents when the reference scale was raised from an HPLC method with a normal range of 3.0% to 4.6% to the DCCT standard (normal range 4.1%–5.7%) in 1992.

But when the reference was lowered in 1997 to the Swedish national standard (normal range 3.1%–4.6%), the patients' control deteriorated by 0.5% and remained at that level for 2–3 years, despite extensive educational efforts. The findings suggest that “the psychological impact of the absolute numbers is very high when even small changes are made to the patients' reference levels,” Dr. Ragnar Hanas of Uddevalla Hospital, in Sweden, concluded (Diabetes Care 2002;25:2110–1).

Noted Dr. Sacks, “At this point, nobody thinks it's a good idea to lower the numbers. … Whatever we do, it will be done in such a way as to not compromise patient care.” However, he said, another option being considered is to report the new IFCC values in mmol/L, rather than as a percentage.

Alternatively, the working group could decide that both A_1c and mean blood glucose be reported—either permanently or for a transition period—similar to the way laboratories now report both creatinine clearance and estimated glomerular filtration rate based on creatinine. How A_1c would be reported in that scenario is also undecided. “It's not clear what will be reported. … All options are still on the table,” Dr. Sacks said.

The timetable for all this to happen is similarly hazy. Dr. Kahn believes it could occur as soon as the end of 2007 or early 2008, based on the assumption that the interim data to be presented in June will allow for a good prediction of the final results, while manufacturers have indicated it would take about 6–9 months to change the settings on the instruments.

But Dr. Sacks is more cautious, estimating that it would take at least a year beyond the final study report in September to analyze the results and, if a change is made, to undertake what will need to be a “huge public education effort.”

Dr. Kahn believes that a change to mean blood glucose would ultimately benefit patients, many of whom are still unclear as to how something called “hemoglobin A_1c,” expressed as a small percentage, relates to the daily readings on their blood glucose monitors.

“People are doing meter readings and getting numbers like 130 or 150. … They say, 'What's that got to do with an 8?' It's all very confusing,” he said.

Dr. Kahn is already preparing for the public education campaign: “I have a book on how [the European Union] converted to the Euro. That's the best analogy.”

'Nothing will be changed without people being notified and given lots of preparation time.' DR. SACKS

The days of hemoglobin A_1c reporting may be numbered.

If the final results of the 11-center International HbA_1c/Mean Blood Glucose (MBG) Study demonstrate that hemoglobin A_1c levels can be mathematically correlated with equivalent mean blood glucose levels in all diabetic populations, a decision could be made as early as 2008 for laboratories to drop A_1c entirely and simply report patients' mean blood glucose instead.

For many in the diabetes community, the move would be a positive one. “People can relate to average blood glucose. The term hemoglobin A_1c is extremely confusing,” said Richard Kahn, Ph.D., chief scientific officer of the American Diabetes Association (ADA).

But any decision to change the way glycemia is reported will be made very carefully, with full awareness of the potentially enormous impact on physicians and patients, according to Dr. David B. Sacks, a pathologist at Brigham and Women's Hospital and Harvard Medical School, Boston, who has been involved in the process from the laboratory medicine side. “We don't want to scare people. Nothing will be changed without people being notified and given lots of preparation time.”

Preliminary study data suggest a correlation tight enough to provide an equation to translate HbA_1c values to equivalent mean blood glucose, Dr. Robert J. Heine, director of the Diabetes Center at Vrije University, Amsterdam, reported in December at the International Diabetes Federation (IDF) meeting in Cape Town, South Africa. Interim data will be presented at the American Diabetes Association's annual Scientific Sessions in June 2007 in Chicago, and final results will be announced at the annual meeting of the European Association for the Study of Diabetes (EASD), to be held in Amsterdam in September 2007.

The study was prompted by the recent adoption of a new reference method for the measurement of hemoglobin A_1c in human blood by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Whereas previous assays utilized only high-performance liquid chromatography (HPLC) to separate glycated from nonglycated hemoglobin, the new method adds a second step involving mass spectroscopy, which further filters out various glycated peptides that are not actually A_1c (Clin. Chem. Lab. Med. 2002;40:78–89).

The result, a more “pure” measure of HbA_1c, is about 1.3%–1.9% lower: A 7% with the old reference method, for example, is 5.3% with the new IFCC method, Dr. Sacks said.

Realizing that a switch to reporting the new numbers would likely generate mass confusion, the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation convened a 14-member working group in 2004 to determine how to proceed. Early on, they agreed unanimously that the same HbA_1c values should be reported globally and that laboratory instrument manufacturers should not make any changes to the current method of A_1c reporting until sufficient data could be collected to link HbA_1c with mean blood glucose. Planning for the International HbA_1c/MBG Study subsequently began in January 2005.

The new two-step IFCC reference method has been in place for about a year. It is not used with actual patient samples because of cost and time constraints. Rather, manufacturers use the values generated by it to calibrate their laboratory A_1c assays, which for the time being are still programmed to report the familiar A_1c numbers. But those settings could be changed, depending on what the working group decides.

Among the options the working group will consider, switching to mean blood glucose reporting alone appears to be the most likely if the results of the International HbA_1c/MBG Study are definitive. A collaboration of the ADA and the EASD, the study is “supported by generous educational grants” from Minimed-Medtronic, Lifescan, Hemocue, Sanofi-Aventis, Abbott Diabetes Care, GlaxoSmithKline, Bayer, and Merck & Co. It involves 300 patients each with type 1 and type 2 diabetes and 100 nondiabetic subjects from six U.S. cities, the Netherlands, Italy, Denmark, India, and Cameroon.

Glycemia is measured by a continuous glucose monitoring system (CGMS) for 2 days every month for 4 months, along with an eight-point self-monitoring daily profile during the CGMS days. Subjects also perform self-monitoring of blood glucose four times daily for a minimum of 3 days a week. Hemoglobin A_1c is measured every month for 4 months.

The aim is to establish the mathematical correlation between A_1c and mean blood glucose across diabetes types, genders, and ethnicities. Although there are existing data correlating HbA_1c with mean blood glucose—and indeed, many laboratories currently report both numbers—those values were generated from old studies using only infrequent finger-stick monitoring, Dr. Heine explained at the IDF meeting.

If the mean blood glucose study does not generate adequate data—or if other factors intervene—the working group will consider other options. The simplest would be to do nothing, leaving the current A_1c values in place. While that would mean continuing to report numbers that aren't totally accurate, it would have the distinct advantage of not rocking the boat.

Moreover, the current A_1c values are directly traceable to outcomes from both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study, allowing for risk assessment for the diabetes-related complications observed in those landmark trials.

Far less likely is a decision to switch to reporting the lower IFCC numbers as percentages. Although some IFCC members had initially pushed for that, the majority have now come to realize that it would just cause too much confusion, Dr. Sacks said.

In addition, there is actually evidence to suggest that lowering the reported A_1c values might even worsen diabetes control. A study done in Sweden, where reported A_1c values were changed twice during the 1990s, showed that glucose control actually improved by about 0.5% among 49 children and adolescents when the reference scale was raised from an HPLC method with a normal range of 3.0% to 4.6% to the DCCT standard (normal range 4.1%–5.7%) in 1992.

But when the reference was lowered in 1997 to the Swedish national standard (normal range 3.1%–4.6%), the patients' control deteriorated by 0.5% and remained at that level for 2–3 years, despite extensive educational efforts. The findings suggest that “the psychological impact of the absolute numbers is very high when even small changes are made to the patients' reference levels,” Dr. Ragnar Hanas of Uddevalla Hospital, in Sweden, concluded (Diabetes Care 2002;25:2110–1).

Noted Dr. Sacks, “At this point, nobody thinks it's a good idea to lower the numbers. … Whatever we do, it will be done in such a way as to not compromise patient care.” However, he said, another option being considered is to report the new IFCC values in mmol/L, rather than as a percentage.

Alternatively, the working group could decide that both A_1c and mean blood glucose be reported—either permanently or for a transition period—similar to the way laboratories now report both creatinine clearance and estimated glomerular filtration rate based on creatinine. How A_1c would be reported in that scenario is also undecided. “It's not clear what will be reported. … All options are still on the table,” Dr. Sacks said.

The timetable for all this to happen is similarly hazy. Dr. Kahn believes it could occur as soon as the end of 2007 or early 2008, based on the assumption that the interim data to be presented in June will allow for a good prediction of the final results, while manufacturers have indicated it would take about 6–9 months to change the settings on the instruments.

But Dr. Sacks is more cautious, estimating that it would take at least a year beyond the final study report in September to analyze the results and, if a change is made, to undertake what will need to be a “huge public education effort.”

Dr. Kahn believes that a change to mean blood glucose would ultimately benefit patients, many of whom are still unclear as to how something called “hemoglobin A_1c,” expressed as a small percentage, relates to the daily readings on their blood glucose monitors.

“People are doing meter readings and getting numbers like 130 or 150. … They say, 'What's that got to do with an 8?' It's all very confusing,” he said.

Dr. Kahn is already preparing for the public education campaign: “I have a book on how [the European Union] converted to the Euro. That's the best analogy.”

'Nothing will be changed without people being notified and given lots of preparation time.' DR. SACKS

The days of hemoglobin A_1c reporting may be numbered.

If the final results of the 11-center International HbA_1c/Mean Blood Glucose (MBG) Study demonstrate that hemoglobin A_1c levels can be mathematically correlated with equivalent mean blood glucose levels in all diabetic populations, a decision could be made as early as 2008 for laboratories to drop A_1c entirely and simply report patients' mean blood glucose instead.

For many in the diabetes community, the move would be a positive one. “People can relate to average blood glucose. The term hemoglobin A_1c is extremely confusing,” said Richard Kahn, Ph.D., chief scientific officer of the American Diabetes Association (ADA).

But any decision to change the way glycemia is reported will be made very carefully, with full awareness of the potentially enormous impact on physicians and patients, according to Dr. David B. Sacks, a pathologist at Brigham and Women's Hospital and Harvard Medical School, Boston, who has been involved in the process from the laboratory medicine side. “We don't want to scare people. Nothing will be changed without people being notified and given lots of preparation time.”

Preliminary study data suggest a correlation tight enough to provide an equation to translate HbA_1c values to equivalent mean blood glucose, Dr. Robert J. Heine, director of the Diabetes Center at Vrije University, Amsterdam, reported in December at the International Diabetes Federation (IDF) meeting in Cape Town, South Africa. Interim data will be presented at the American Diabetes Association's annual Scientific Sessions in June 2007 in Chicago, and final results will be announced at the annual meeting of the European Association for the Study of Diabetes (EASD), to be held in Amsterdam in September 2007.

The study was prompted by the recent adoption of a new reference method for the measurement of hemoglobin A_1c in human blood by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Whereas previous assays utilized only high-performance liquid chromatography (HPLC) to separate glycated from nonglycated hemoglobin, the new method adds a second step involving mass spectroscopy, which further filters out various glycated peptides that are not actually A_1c (Clin. Chem. Lab. Med. 2002;40:78–89).

The result, a more “pure” measure of HbA_1c, is about 1.3%–1.9% lower: A 7% with the old reference method, for example, is 5.3% with the new IFCC method, Dr. Sacks said.

Realizing that a switch to reporting the new numbers would likely generate mass confusion, the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation convened a 14-member working group in 2004 to determine how to proceed. Early on, they agreed unanimously that the same HbA_1c values should be reported globally and that laboratory instrument manufacturers should not make any changes to the current method of A_1c reporting until sufficient data could be collected to link HbA_1c with mean blood glucose. Planning for the International HbA_1c/MBG Study subsequently began in January 2005.

The new two-step IFCC reference method has been in place for about a year. It is not used with actual patient samples because of cost and time constraints. Rather, manufacturers use the values generated by it to calibrate their laboratory A_1c assays, which for the time being are still programmed to report the familiar A_1c numbers. But those settings could be changed, depending on what the working group decides.

Among the options the working group will consider, switching to mean blood glucose reporting alone appears to be the most likely if the results of the International HbA_1c/MBG Study are definitive. A collaboration of the ADA and the EASD, the study is “supported by generous educational grants” from Minimed-Medtronic, Lifescan, Hemocue, Sanofi-Aventis, Abbott Diabetes Care, GlaxoSmithKline, Bayer, and Merck & Co. It involves 300 patients each with type 1 and type 2 diabetes and 100 nondiabetic subjects from six U.S. cities, the Netherlands, Italy, Denmark, India, and Cameroon.

Glycemia is measured by a continuous glucose monitoring system (CGMS) for 2 days every month for 4 months, along with an eight-point self-monitoring daily profile during the CGMS days. Subjects also perform self-monitoring of blood glucose four times daily for a minimum of 3 days a week. Hemoglobin A_1c is measured every month for 4 months.

The aim is to establish the mathematical correlation between A_1c and mean blood glucose across diabetes types, genders, and ethnicities. Although there are existing data correlating HbA_1c with mean blood glucose—and indeed, many laboratories currently report both numbers—those values were generated from old studies using only infrequent finger-stick monitoring, Dr. Heine explained at the IDF meeting.

If the mean blood glucose study does not generate adequate data—or if other factors intervene—the working group will consider other options. The simplest would be to do nothing, leaving the current A_1c values in place. While that would mean continuing to report numbers that aren't totally accurate, it would have the distinct advantage of not rocking the boat.

Moreover, the current A_1c values are directly traceable to outcomes from both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study, allowing for risk assessment for the diabetes-related complications observed in those landmark trials.

Far less likely is a decision to switch to reporting the lower IFCC numbers as percentages. Although some IFCC members had initially pushed for that, the majority have now come to realize that it would just cause too much confusion, Dr. Sacks said.

In addition, there is actually evidence to suggest that lowering the reported A_1c values might even worsen diabetes control. A study done in Sweden, where reported A_1c values were changed twice during the 1990s, showed that glucose control actually improved by about 0.5% among 49 children and adolescents when the reference scale was raised from an HPLC method with a normal range of 3.0% to 4.6% to the DCCT standard (normal range 4.1%–5.7%) in 1992.

But when the reference was lowered in 1997 to the Swedish national standard (normal range 3.1%–4.6%), the patients' control deteriorated by 0.5% and remained at that level for 2–3 years, despite extensive educational efforts. The findings suggest that “the psychological impact of the absolute numbers is very high when even small changes are made to the patients' reference levels,” Dr. Ragnar Hanas of Uddevalla Hospital, in Sweden, concluded (Diabetes Care 2002;25:2110–1).

Noted Dr. Sacks, “At this point, nobody thinks it's a good idea to lower the numbers. … Whatever we do, it will be done in such a way as to not compromise patient care.” However, he said, another option being considered is to report the new IFCC values in mmol/L, rather than as a percentage.

Alternatively, the working group could decide that both A_1c and mean blood glucose be reported—either permanently or for a transition period—similar to the way laboratories now report both creatinine clearance and estimated glomerular filtration rate based on creatinine. How A_1c would be reported in that scenario is also undecided. “It's not clear what will be reported. … All options are still on the table,” Dr. Sacks said.

The timetable for all this to happen is similarly hazy. Dr. Kahn believes it could occur as soon as the end of 2007 or early 2008, based on the assumption that the interim data to be presented in June will allow for a good prediction of the final results, while manufacturers have indicated it would take about 6–9 months to change the settings on the instruments.

But Dr. Sacks is more cautious, estimating that it would take at least a year beyond the final study report in September to analyze the results and, if a change is made, to undertake what will need to be a “huge public education effort.”

Dr. Kahn believes that a change to mean blood glucose would ultimately benefit patients, many of whom are still unclear as to how something called “hemoglobin A_1c,” expressed as a small percentage, relates to the daily readings on their blood glucose monitors.

“People are doing meter readings and getting numbers like 130 or 150. … They say, 'What's that got to do with an 8?' It's all very confusing,” he said.

Dr. Kahn is already preparing for the public education campaign: “I have a book on how [the European Union] converted to the Euro. That's the best analogy.”

'Nothing will be changed without people being notified and given lots of preparation time.' DR. SACKS

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Ms. Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

In September 2006, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]).

Kaiser Permanente, the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“Yes, we have the capacity to do it, and yes, we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the U.S. population, including more than 16,000 active HIV-infected patients.

Nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. Once diagnosed, however, more than 90% enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other barriers to expanded HIV screening include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening. While most managed care organizations support targeted screening for pregnant women and for individuals with high-risk behavior, they have not generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states Kaiser serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, counseling, and patient education. “Testing in [Kaiser Permanente/Group Health Cooperative] is the desired norm. … We are uncomfortable screening without a proper testing process,” Dr. Horberg said.

But, he added, despite the potential roadblocks, “We are confident we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Since the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care, but this service is “optional.” A recent study by George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done. There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain.”

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes the federal government must contribute more to Medicaid to implement the CDC guidelines, noting: “It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments [will] be adequate. … Medicaid, with its significant reach into low-income populations and ethnic/racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs.”

'Yes, we have the capacity to do [routine screening], and yes, we have the will to do it. But it is a lot of money.' DR. HORBERG

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Ms. Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

In September 2006, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]).

Kaiser Permanente, the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“Yes, we have the capacity to do it, and yes, we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the U.S. population, including more than 16,000 active HIV-infected patients.

Nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. Once diagnosed, however, more than 90% enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other barriers to expanded HIV screening include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening. While most managed care organizations support targeted screening for pregnant women and for individuals with high-risk behavior, they have not generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states Kaiser serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, counseling, and patient education. “Testing in [Kaiser Permanente/Group Health Cooperative] is the desired norm. … We are uncomfortable screening without a proper testing process,” Dr. Horberg said.

But, he added, despite the potential roadblocks, “We are confident we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Since the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care, but this service is “optional.” A recent study by George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done. There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain.”

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes the federal government must contribute more to Medicaid to implement the CDC guidelines, noting: “It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments [will] be adequate. … Medicaid, with its significant reach into low-income populations and ethnic/racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs.”

'Yes, we have the capacity to do [routine screening], and yes, we have the will to do it. But it is a lot of money.' DR. HORBERG

WASHINGTON — Reimbursement for routine, universal HIV screening will prove challenging in both the private and public sectors, Dr. Michael Horberg and Ms. Christine Lubinski said in separate presentations at a meeting on HIV diagnosis and prevention and access to care.

In September 2006, the Centers for Disease Control and Prevention recommended that diagnostic HIV testing and “opt-out” HIV screening be made a part of routine clinical care in all health care settings for patients aged 13–64 years (MMWR 2006;55[RR-14]).

Kaiser Permanente, the country's largest staff-model HMO, is “grappling with this now. We have to look at the implications,” said Dr. Horberg, director of HIV/AIDS Policy, Quality Improvement, and Research at Kaiser.

“Yes, we have the capacity to do it, and yes, we have the will to do it. But it is a lot of money,” said Dr. Horberg.

As for the public sector, “There are significant roadblocks. … The Centers for Medicare and Medicaid Services and the [Bush] administration have little commitment to expand the federal contribution to the Medicaid program in any way, shape, or form,” said Ms. Lubinski, executive director of the HIV Medicine Association. This association is a multidisciplinary arm of the Infectious Diseases Society of America that represents medical professionals involved in HIV care.

However, a few states—most notably New Jersey—have committed their Medicaid funds to cover broad-based HIV testing for low-income beneficiaries, Ms. Lubinski noted.

The Kaiser Permanente/Group Health Cooperative system covers approximately 3% of the U.S. population, including more than 16,000 active HIV-infected patients.

Nearly two-thirds of HIV-infected patients within Kaiser are not diagnosed until they meet AIDS criteria, “which means our case-finding is not very good,” Dr. Horberg remarked. Once diagnosed, however, more than 90% enter into care within 120 days of diagnosis. Last year, more than 70% of those patients were on highly active antiretroviral therapy, he said.

Kaiser has been performing about 340,000 HIV antibody tests a year, which account for 15% of its target population aged 13–65 years. The majority are pregnant women, of whom more than 90% are currently tested. If Kaiser were to adopt the CDC guidelines, it would mean about 5 million more tests—and 1,773 newly identified cases—at a cost of at least $26,599,450 annually.

Aside from cost, other barriers to expanded HIV screening include the fact that many managed care organizations follow recommendations from the U.S. Preventive Services Task Force, not the CDC, in determining what type of tests to cover. The USPSTF has not yet issued guidelines on universal HIV screening. While most managed care organizations support targeted screening for pregnant women and for individuals with high-risk behavior, they have not generated broader screening policies. “Most are probably waiting for the USPSTF,” Dr. Horberg said.

The CDC's provision that prevention counseling should not be required as part of HIV screening is already posing problems in states that require informed consent for HIV testing, including many of the states Kaiser serves. Kaiser differentiates between “screening,” defined as testing without counseling, and “testing,” which includes the HIV antibody test, counseling, and patient education. “Testing in [Kaiser Permanente/Group Health Cooperative] is the desired norm. … We are uncomfortable screening without a proper testing process,” Dr. Horberg said.

But, he added, despite the potential roadblocks, “We are confident we can handle all new HIV-infected patients identified.”

The public sector is another story. It would take an act of Congress before Medicare, which has only recently begun to cover any preventive health services, would cover HIV screening. Since the upper target age of the CDC recommendation is 64 years, the only people for whom Medicare would cover screening are the 6.8 million current beneficiaries under age 65 who qualify by disability, Ms. Lubinski said.

Thus, the bulk of the reimbursement for HIV screening would fall to Medicaid, which currently provides health coverage to about half of all people with AIDS in the United States and a significant number of those newly diagnosed with HIV. In an analysis done in 25 states, 22% of HIV-infected individuals were already Medicaid eligible at the time of diagnosis.

Federal law allows HIV screening to be covered by states either under fee-for-service or Medicaid managed care, but this service is “optional.” A recent study by George Washington University's Center for Health Services Research and Policy found that Medicaid programs in 32 of the 48 states surveyed covered targeted HIV testing and counseling. A few state programs also covered services such as HIV risk assessment and case management.

But as yet, with the exception of New Jersey, most state Medicaid programs have not adopted routine HIV testing. California has employed a special waiver to provide broad family planning services including HIV testing and counseling for men and women of childbearing age up to 200% of the poverty level. However, that type of waiver is unlikely to be granted elsewhere, she noted.

States could opt to cover HIV screening under a “diagnostic, screening, preventive, and rehabilitative” (DSPR) benefit. The state would need to broaden the definition of medical necessity to allow for preventive services such as HIV screening, as Massachusetts has done. There, a service is “medically necessary if it is reasonably calculated to prevent, diagnose, prevent the worsening of, alleviate, correct, or cure conditions in the member that endanger life, or cause suffering or pain.”

Such definitions could theoretically make HIV testing and counseling eligible for reimbursement, Ms. Lubinski said.

She said she believes the federal government must contribute more to Medicaid to implement the CDC guidelines, noting: “It is absolutely unreasonable to think that the modest amount of discretionary funding through the CDC, Ryan White [Comprehensive AIDS Resources Emergency Act], or state and local health departments [will] be adequate. … Medicaid, with its significant reach into low-income populations and ethnic/racial minorities, must be part of the financing mix. Federal leadership could and should facilitate coverage of routine screening by state Medicaid programs.”

'Yes, we have the capacity to do [routine screening], and yes, we have the will to do it. But it is a lot of money.' DR. HORBERG