Diana Mahoney

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines advise antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet a statistical model estimates only 56% of eligible patients likely received it, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of the eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving the recommended antiretroviral treatment include the expense of multidrug cocktails, which can cost more than $10,000 a year. Although private insurance often covers this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to narrow the scope of the problem should be implemented without waiting for more research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more effective methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines advise antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet a statistical model estimates only 56% of eligible patients likely received it, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of the eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving the recommended antiretroviral treatment include the expense of multidrug cocktails, which can cost more than $10,000 a year. Although private insurance often covers this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to narrow the scope of the problem should be implemented without waiting for more research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more effective methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Almost half of HIV-positive individuals in the United States who meet federal guidelines for antiretroviral therapy may not be receiving the treatment, according to a recent estimate by the Centers for Disease Control and Prevention.

Late diagnoses, unawareness of HIV risk factors and risk status, and treatment inaccessibility are among the likely factors contributing to the insufficient care of as many as 44% of the country's treatment-eligible HIV-positive individuals, CDC medical epidemiologist Eyasu Teshale, M.D., reported at a conference on retroviruses and opportunistic infections.

Using data from an analysis of AIDS diagnoses reported by all 50 states and HIV diagnoses reported by 30 states with well-established integrated HIV/AIDS reporting systems and lab-based CD4 reports, the CDC investigators estimated that, through 2003, there were about 480,000 treatment-eligible HIV/AIDS patients in this country.

Federal treatment guidelines advise antiretroviral therapy for HIV-infected patients with CD4 white blood cell counts of 350 cells/μL or lower; yet a statistical model estimates only 56% of eligible patients likely received it, said Dr. Teshale.

To estimate the number of HIV/AIDS patients receiving antiretroviral therapy, the CDC investigators extrapolated treatment percentages from CDC's Adult/Adolescent Spectrum of HIV Disease (ASD) project, a 10-city medical records-based surveillance project that prospectively collected information from more than 60,000 HIV/AIDS patients from 1990 through June 2004.

About 79% of the HIV-infected patients in the ASD population with CD4 counts below 350 cells/μL received antiretroviral therapy. “We applied that proportion to the 340,000 patients estimated to be 'in care' on a national level,” Dr. Teshale said. Using this approach, the investigators estimated that 268,000 (79%) of the 340,000 patients diagnosed and receiving care in the U.S. received ART at the end of 2003. These 268,000 people represent only about 56% of the 480,000 Americans aged 15-49 who were living with HIV/AIDS and were eligible for ART at the end of 2003.

An estimated 42% of the eligible patients not getting antiretroviral therapy have not even been diagnosed with HIV infection, and as many as 25% are likely aware of their HIV status but are not receiving medical care for it, Dr. Teshale said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Among patients who have access to health care and are being treated for HIV, barriers to receiving the recommended antiretroviral treatment include the expense of multidrug cocktails, which can cost more than $10,000 a year. Although private insurance often covers this expense, patients receiving public health assistance are often placed on waiting lists for the drugs. Finally, some patients choose not to take the medications because of the side effects.

The new estimates, though limited by variations in data collection by states and inconsistencies in the medical records included in the analyses, support previous research demonstrating the unmet need for antiretroviral therapy.

The findings need to be validated by additional research, and the factors contributing to insufficient care for HIV-infected individuals deserve more study.

However, efforts to narrow the scope of the problem should be implemented without waiting for more research, Dr. Teshale said. These include increasing individuals' awareness of their HIV status, providing more effective methods for linking at-risk individuals to prevention and care programs, and encouraging health care providers to prescribe antiretroviral therapy, according to federal guidelines.

BOSTON — Switching antiretroviral medications can reduce the incidence and severity of drug-induced lipoatrophy in some HIV patients, according to three studies presented at a conference on retroviruses and opportunistic infections.

Subcutaneous fat loss, particularly from the face and limbs, is a frequent adverse effect of current combination antiretroviral therapy (ART) regimens. Although the effect has been associated with both nucleoside analogue reverse transcriptase inhibitors (NRTI) and protease inhibitors, not all of the drugs in both classes are equal in this regard, prompting investigators to consider new combinations that might have more favorable effects on fat distribution.

Switching to Abacavir or Tenofovir

In one study—a 48-week randomized, open-label trial—Graeme Moyle, M.D., of the Royal Free Hospital, London, and colleagues tested the hypothesis that removing a thymidine analogue from a highly active ART (HAART) regimen may improve associated lipoatrophy.

The investigators studied changes in limb fat as measured by dual energy x-ray absorptiometry (DXA) and visceral fat as measured by computed tomography in 105 HIV-infected adults in whom zidovudine (AZT, Retrovir) or stavudine (d4T, Zerit) therapy was replaced with either the nucleoside analogue abacavir (Ziagen) or the NRTI tenofovir (Viread).

Of the 71 stavudine and 34 zidovudine patients, 53 were randomly assigned to abacavir, and 52 were assigned to tenofovir. At 48 months, patients in both groups had similarly significant increases in leg and visceral fat from baseline, Dr. Moyle reported in an abstract presentation at the conference sponsored by the Foundation for Retrovirology and Human Health.

Among patients switched to abacavir, limb fat had increased at the end of the study by an average of 0.5 kg from a baseline average of 3.7 kg. In the tenofovir group, limb fat increased 0.3 kg from a baseline average of 3.9 kg. “Similar changes were observed in visceral and subcutaneous abdominal fat,” Dr. Moyle said.

Both treatment groups maintained similar virologic suppression with the change in their regimens, although more patients in the abacavir group than in the tenofovir group discontinued therapy. Of the patients switched to abacavir, eight discontinued treatment, including three who developed hypersensitivity reactions. Three patients in the tenofovir arm dropped out of the study.

There were no statistically significant differences between treatment groups with respect to changes in bone mineral density scores, but measurements of mean changes in total cholesterol, LDL cholesterol, and triglycerides through week 48 significantly favored tenofovir.

Nucleoside-Sparing Regimens I

Mirroring these findings were the results from a prospective, randomized trial presented by Robert Murphy, M.D., of Northwestern University, Chicago on behalf of the AACTG 5110 Study Team.

In the first study to detect an improvement in lipoatrophy after only 24 weeks of treatment modification, 101 patients on zidovudine-inclusive or stavudine-inclusive regimens were randomized to either change their nucleoside to abacavir, switch to a nucleoside-sparing cocktail of ritonavir (Norvir)-boosted lopinavir (Kaletra) plus nevirapine (Viramune), or delay any switch until 24 weeks followed by randomization into one of the two treatment groups.

At 24 weeks, CT-measured limb fat among patients on the nucleoside-sparing regimen had increased 8%, while no change was observed in the abacavir group and a 3% increase was found in the treatment-delay group. Both treatment groups had significant increases in subcutaneous abdominal fat—17% for the nucleoside-sparing group and 9% for the abacavir group—compared with a decrease in the treatment-delay group. Visceral abdominal fat decreased in all three groups, with a smaller decrease in the nucleoside-sparing group than in the abacavir group (9% vs. 12%).

Virologic suppression was maintained in both treatment groups. “The [nucleoside-sparing] regimen led to a significant increase in CD4 cell count at 24 weeks,” Dr. Murphy said, compared with a nonsignificant decrease with abacavir. Similar proportions of both treatment groups maintained undetectable viral loads.

Although statistically significant, “the 8% increase in limb fat from a very low baseline [median 18.9 cm

Nucleoside-Sparing Regimens II

Similar results were reported from a longer-term study in which 62 patients who had been on indinavir (Crixivan)/efavirenz (Sustiva) regimens for at least 18 months were randomly switched to either efavirenz and two nucleosides or to ritonavir-boosted lopinavir and efavirenz.

At baseline, median total limb fat for all patients, measured by DXA, was 6 kg. At 48 weeks, limb fat of patients in the non-nucleoside arm had increased significantly by a median of 562 g, compared with a 246-g loss in the nucleoside arm, reported lead investigator Pablo Tebas, M.D., of the University of Pennsylvania, Philadelphia.

At 48 weeks, there were no differences in amount of trunk fat, bone mineral density, or glucose metabolism between the treatment groups. However, total cholesterol and triglyceride levels increased significantly in the nonnucleoside group.

Follow-up data from 46 patients studied for a median of 104 weeks showed a median gain compared with baseline of 782 g of limb fat among the nonnucleoside patients and a median 900-g loss among patients receiving nucleosides.

Even though the median 13% gain in limb fat over 2 years represents a “relatively modest” increase, Dr. Tebas maintained that a switch to a nucleoside-sparing regimen is a valid therapeutic option for HIV patients with lipoatrophy. He warned, however, that the advantages of fat restoration must be weighed against the “inferior virologic potency” of nucleoside-sparing regimens.

Considering the poorly reversible nature of lipoatrophy as well as the fact that ART-induced changes in body-fat distribution can jeopardize the sustained effectiveness of and adherence to treatment, further research into the differences between specific antiretroviral agents within and between drug classes “is imperative,” said plenary speaker Peter Reiss, M.D., of the Academic Medical Center in Amsterdam.

Additionally, insights gleaned from such research “must be allowed to benefit patients and HIV treatment programs worldwide,” Dr. Reiss concluded.

BOSTON — Switching antiretroviral medications can reduce the incidence and severity of drug-induced lipoatrophy in some HIV patients, according to three studies presented at a conference on retroviruses and opportunistic infections.

Subcutaneous fat loss, particularly from the face and limbs, is a frequent adverse effect of current combination antiretroviral therapy (ART) regimens. Although the effect has been associated with both nucleoside analogue reverse transcriptase inhibitors (NRTI) and protease inhibitors, not all of the drugs in both classes are equal in this regard, prompting investigators to consider new combinations that might have more favorable effects on fat distribution.

Switching to Abacavir or Tenofovir

In one study—a 48-week randomized, open-label trial—Graeme Moyle, M.D., of the Royal Free Hospital, London, and colleagues tested the hypothesis that removing a thymidine analogue from a highly active ART (HAART) regimen may improve associated lipoatrophy.

The investigators studied changes in limb fat as measured by dual energy x-ray absorptiometry (DXA) and visceral fat as measured by computed tomography in 105 HIV-infected adults in whom zidovudine (AZT, Retrovir) or stavudine (d4T, Zerit) therapy was replaced with either the nucleoside analogue abacavir (Ziagen) or the NRTI tenofovir (Viread).

Of the 71 stavudine and 34 zidovudine patients, 53 were randomly assigned to abacavir, and 52 were assigned to tenofovir. At 48 months, patients in both groups had similarly significant increases in leg and visceral fat from baseline, Dr. Moyle reported in an abstract presentation at the conference sponsored by the Foundation for Retrovirology and Human Health.

Among patients switched to abacavir, limb fat had increased at the end of the study by an average of 0.5 kg from a baseline average of 3.7 kg. In the tenofovir group, limb fat increased 0.3 kg from a baseline average of 3.9 kg. “Similar changes were observed in visceral and subcutaneous abdominal fat,” Dr. Moyle said.

Both treatment groups maintained similar virologic suppression with the change in their regimens, although more patients in the abacavir group than in the tenofovir group discontinued therapy. Of the patients switched to abacavir, eight discontinued treatment, including three who developed hypersensitivity reactions. Three patients in the tenofovir arm dropped out of the study.

There were no statistically significant differences between treatment groups with respect to changes in bone mineral density scores, but measurements of mean changes in total cholesterol, LDL cholesterol, and triglycerides through week 48 significantly favored tenofovir.

Nucleoside-Sparing Regimens I

Mirroring these findings were the results from a prospective, randomized trial presented by Robert Murphy, M.D., of Northwestern University, Chicago on behalf of the AACTG 5110 Study Team.

In the first study to detect an improvement in lipoatrophy after only 24 weeks of treatment modification, 101 patients on zidovudine-inclusive or stavudine-inclusive regimens were randomized to either change their nucleoside to abacavir, switch to a nucleoside-sparing cocktail of ritonavir (Norvir)-boosted lopinavir (Kaletra) plus nevirapine (Viramune), or delay any switch until 24 weeks followed by randomization into one of the two treatment groups.

At 24 weeks, CT-measured limb fat among patients on the nucleoside-sparing regimen had increased 8%, while no change was observed in the abacavir group and a 3% increase was found in the treatment-delay group. Both treatment groups had significant increases in subcutaneous abdominal fat—17% for the nucleoside-sparing group and 9% for the abacavir group—compared with a decrease in the treatment-delay group. Visceral abdominal fat decreased in all three groups, with a smaller decrease in the nucleoside-sparing group than in the abacavir group (9% vs. 12%).

Virologic suppression was maintained in both treatment groups. “The [nucleoside-sparing] regimen led to a significant increase in CD4 cell count at 24 weeks,” Dr. Murphy said, compared with a nonsignificant decrease with abacavir. Similar proportions of both treatment groups maintained undetectable viral loads.

Although statistically significant, “the 8% increase in limb fat from a very low baseline [median 18.9 cm

Nucleoside-Sparing Regimens II

Similar results were reported from a longer-term study in which 62 patients who had been on indinavir (Crixivan)/efavirenz (Sustiva) regimens for at least 18 months were randomly switched to either efavirenz and two nucleosides or to ritonavir-boosted lopinavir and efavirenz.

At baseline, median total limb fat for all patients, measured by DXA, was 6 kg. At 48 weeks, limb fat of patients in the non-nucleoside arm had increased significantly by a median of 562 g, compared with a 246-g loss in the nucleoside arm, reported lead investigator Pablo Tebas, M.D., of the University of Pennsylvania, Philadelphia.

At 48 weeks, there were no differences in amount of trunk fat, bone mineral density, or glucose metabolism between the treatment groups. However, total cholesterol and triglyceride levels increased significantly in the nonnucleoside group.

Follow-up data from 46 patients studied for a median of 104 weeks showed a median gain compared with baseline of 782 g of limb fat among the nonnucleoside patients and a median 900-g loss among patients receiving nucleosides.

Even though the median 13% gain in limb fat over 2 years represents a “relatively modest” increase, Dr. Tebas maintained that a switch to a nucleoside-sparing regimen is a valid therapeutic option for HIV patients with lipoatrophy. He warned, however, that the advantages of fat restoration must be weighed against the “inferior virologic potency” of nucleoside-sparing regimens.

Considering the poorly reversible nature of lipoatrophy as well as the fact that ART-induced changes in body-fat distribution can jeopardize the sustained effectiveness of and adherence to treatment, further research into the differences between specific antiretroviral agents within and between drug classes “is imperative,” said plenary speaker Peter Reiss, M.D., of the Academic Medical Center in Amsterdam.

Additionally, insights gleaned from such research “must be allowed to benefit patients and HIV treatment programs worldwide,” Dr. Reiss concluded.

BOSTON — Switching antiretroviral medications can reduce the incidence and severity of drug-induced lipoatrophy in some HIV patients, according to three studies presented at a conference on retroviruses and opportunistic infections.

Subcutaneous fat loss, particularly from the face and limbs, is a frequent adverse effect of current combination antiretroviral therapy (ART) regimens. Although the effect has been associated with both nucleoside analogue reverse transcriptase inhibitors (NRTI) and protease inhibitors, not all of the drugs in both classes are equal in this regard, prompting investigators to consider new combinations that might have more favorable effects on fat distribution.

Switching to Abacavir or Tenofovir

In one study—a 48-week randomized, open-label trial—Graeme Moyle, M.D., of the Royal Free Hospital, London, and colleagues tested the hypothesis that removing a thymidine analogue from a highly active ART (HAART) regimen may improve associated lipoatrophy.

The investigators studied changes in limb fat as measured by dual energy x-ray absorptiometry (DXA) and visceral fat as measured by computed tomography in 105 HIV-infected adults in whom zidovudine (AZT, Retrovir) or stavudine (d4T, Zerit) therapy was replaced with either the nucleoside analogue abacavir (Ziagen) or the NRTI tenofovir (Viread).

Of the 71 stavudine and 34 zidovudine patients, 53 were randomly assigned to abacavir, and 52 were assigned to tenofovir. At 48 months, patients in both groups had similarly significant increases in leg and visceral fat from baseline, Dr. Moyle reported in an abstract presentation at the conference sponsored by the Foundation for Retrovirology and Human Health.

Among patients switched to abacavir, limb fat had increased at the end of the study by an average of 0.5 kg from a baseline average of 3.7 kg. In the tenofovir group, limb fat increased 0.3 kg from a baseline average of 3.9 kg. “Similar changes were observed in visceral and subcutaneous abdominal fat,” Dr. Moyle said.

Both treatment groups maintained similar virologic suppression with the change in their regimens, although more patients in the abacavir group than in the tenofovir group discontinued therapy. Of the patients switched to abacavir, eight discontinued treatment, including three who developed hypersensitivity reactions. Three patients in the tenofovir arm dropped out of the study.

There were no statistically significant differences between treatment groups with respect to changes in bone mineral density scores, but measurements of mean changes in total cholesterol, LDL cholesterol, and triglycerides through week 48 significantly favored tenofovir.

Nucleoside-Sparing Regimens I

Mirroring these findings were the results from a prospective, randomized trial presented by Robert Murphy, M.D., of Northwestern University, Chicago on behalf of the AACTG 5110 Study Team.

In the first study to detect an improvement in lipoatrophy after only 24 weeks of treatment modification, 101 patients on zidovudine-inclusive or stavudine-inclusive regimens were randomized to either change their nucleoside to abacavir, switch to a nucleoside-sparing cocktail of ritonavir (Norvir)-boosted lopinavir (Kaletra) plus nevirapine (Viramune), or delay any switch until 24 weeks followed by randomization into one of the two treatment groups.

At 24 weeks, CT-measured limb fat among patients on the nucleoside-sparing regimen had increased 8%, while no change was observed in the abacavir group and a 3% increase was found in the treatment-delay group. Both treatment groups had significant increases in subcutaneous abdominal fat—17% for the nucleoside-sparing group and 9% for the abacavir group—compared with a decrease in the treatment-delay group. Visceral abdominal fat decreased in all three groups, with a smaller decrease in the nucleoside-sparing group than in the abacavir group (9% vs. 12%).

Virologic suppression was maintained in both treatment groups. “The [nucleoside-sparing] regimen led to a significant increase in CD4 cell count at 24 weeks,” Dr. Murphy said, compared with a nonsignificant decrease with abacavir. Similar proportions of both treatment groups maintained undetectable viral loads.

Although statistically significant, “the 8% increase in limb fat from a very low baseline [median 18.9 cm

Nucleoside-Sparing Regimens II

Similar results were reported from a longer-term study in which 62 patients who had been on indinavir (Crixivan)/efavirenz (Sustiva) regimens for at least 18 months were randomly switched to either efavirenz and two nucleosides or to ritonavir-boosted lopinavir and efavirenz.

At baseline, median total limb fat for all patients, measured by DXA, was 6 kg. At 48 weeks, limb fat of patients in the non-nucleoside arm had increased significantly by a median of 562 g, compared with a 246-g loss in the nucleoside arm, reported lead investigator Pablo Tebas, M.D., of the University of Pennsylvania, Philadelphia.

At 48 weeks, there were no differences in amount of trunk fat, bone mineral density, or glucose metabolism between the treatment groups. However, total cholesterol and triglyceride levels increased significantly in the nonnucleoside group.

Follow-up data from 46 patients studied for a median of 104 weeks showed a median gain compared with baseline of 782 g of limb fat among the nonnucleoside patients and a median 900-g loss among patients receiving nucleosides.

Even though the median 13% gain in limb fat over 2 years represents a “relatively modest” increase, Dr. Tebas maintained that a switch to a nucleoside-sparing regimen is a valid therapeutic option for HIV patients with lipoatrophy. He warned, however, that the advantages of fat restoration must be weighed against the “inferior virologic potency” of nucleoside-sparing regimens.

Considering the poorly reversible nature of lipoatrophy as well as the fact that ART-induced changes in body-fat distribution can jeopardize the sustained effectiveness of and adherence to treatment, further research into the differences between specific antiretroviral agents within and between drug classes “is imperative,” said plenary speaker Peter Reiss, M.D., of the Academic Medical Center in Amsterdam.

Additionally, insights gleaned from such research “must be allowed to benefit patients and HIV treatment programs worldwide,” Dr. Reiss concluded.

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual-energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans. Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scans. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients; among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London. The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%).

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said, suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and vitamin D. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention,” she said.

Much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, but the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” Dr. Koshy said.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual-energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans. Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scans. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients; among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London. The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%).

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said, suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and vitamin D. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention,” she said.

Much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, but the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” Dr. Koshy said.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual-energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans. Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scans. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients; among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London. The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%).

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said, suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and vitamin D. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention,” she said.

Much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, but the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” Dr. Koshy said.

STOWE, VT. — Uncertain triggers, therapeutic controversies, and potentially fatal complications can compromise emergency management of diabetic ketoacidosis, according to Steven M. Hulsey, M.D.

Diabetic ketoacidosis (DKA) is a major, acute metabolic complication of diabetes that requires immediate and intensive care.

Although DKA is not a difficult diagnosis per se—particularly in the context of known type 1 diabetes—evaluation and treatment can be challenging, Dr. Hulsey said at an emergency medicine update sponsored by the University of Vermont.

Diagnosis and management of the severe insulin deficiency that sets the ketoacidotic chain in motion are only half the battle. The other half is identifying the event or condition that precipitated the metabolic disorder and addressing it appropriately to restore normal balance and prevent recurrences.

“Initially, you want to make sure that what is causing the ketoacidosis isn't itself a life-threatening condition, such as myocardial infarction or sepsis,” said Dr. Hulsey, noting that in some cases, the “trigger” could pose at least as great a threat as the DKA.

Excessive urination, severe thirst, fruity-smelling breath, abdominal pain, nausea, vomiting, fatigue, breathing difficulties, and mental confusion are among the telltale symptoms of DKA.

Blood glucose levels higher than 250 mg/dL, large quantities of ketones in the urine and plasma, low serum bicarbonate (less than 15 mmol/L), elevated anion gap (more than 16 mmol/L), and a blood pH of less than 7.3 confirm a diagnosis of DKA.

Because there is no clinically significant difference between arterial and venous pH estimates in patients with DKA, “go ahead and get the venous sample upon insertion of the IV for fluid resuscitation,” Dr. Hulsey recommended. “This spares the patient a painful arterial stick later.”

Severe electrolyte disturbances are also characteristic of DKA. The most dangerous of these, total body potassium loss, is difficult to assess, because it is typically not mirrored in serum potassium levels—a factor that must be considered before treatment.

Initial blood potassium levels usually are normal to high, despite substantial total body potassium deficits. This is because the acidosis encourages leakage of intracellular potassium.

Treatment with insulin—a cornerstone of DKA therapy—drives potassium back into the cells, and levels may drop very quickly.

For this reason, frequent blood potassium checks are critical during therapy.

“If serum potassium levels are even just slightly low on the first test, that means that total body potassium is probably critically low and must be replenished before giving the patient insulin,” Dr. Hulsey said. “If potassium levels are normal, total body potassium is probably low and should be replenished [along with insulin infusion].”

The pillars of DKA treatment include efforts to correct life-threatening dehydration, hyperglycemia, ketonemia and acidemia, and electrolyte disturbances. Toward this end, aggressive fluid resuscitation is warranted unless the patient has signs of any condition, such as congestive heart failure, that might be exacerbated by large volumes of intravenous fluids.

A less aggressive approach is also recommended when treating children and adolescents, who are at greater risk for cerebral edema.

It has been suggested, though not proven, that over-aggressive fluid replacement is linked to this rare, often fatal complication. “But most physicians choose to err on the side of underreplacement in kids,” Dr. Hulsey said.

Intravenous insulin is also indicated, although there is ongoing debate about dosing and infusion rates.

In the past, large doses of insulin were recommended early in DKA therapy. Current thinking is that hyperglycemia should be corrected gradually to avoid hypoglycemia, hypokalemia, and cerebral or pulmonary edema, he said. Blood glucose levels should be monitored hourly, and insulin dose should be adjusted accordingly.

There currently is no consensus on the practice of administering an intravenous bolus of regular insulin as a way to jump-start recovery efforts before low-dose infusion.

“In reality, a bolus dose is not needed [before low-dose infusion] to obtain optimal plasma levels, because the time needed to reach normal glycemic levels is the same,” Dr. Hulsey said. “And there is the possibility that a bolus dose may increase the risk for hypokalemia.”

A bolus dose should be considered, however, when a substantial delay in treatment is anticipated, he said.

In such circumstances, it is not unreasonable to administer successive small bolus doses, as long as potassium levels are being monitored.

The use of intravenous bicarbonate to reduce the immediate risks of extremely low pH is also a contentious topic.

The theoretical advantages include a reduction in cardiac irritability, respiratory discomfort, and intravenous chloride load, while the theoretical disadvantages include the possibility of hypokalemia and arrhythmia and exacerbated intracellular and intracerebral acidosis.

“In reality, there are some studies that have shown that giving bicarbonate in DKA doesn't make a difference either way, so it should probably be avoided” Dr. Hulsey said. Bicarbonate should not be used in pediatric patients, because of a possible association with cerebral edema, he said.

As noted, replacing potassium deficits should be included in the DKA management strategy. The dose will vary depending on serum levels, which should be measured regularly so that the rate of replacement can be adjusted as needed, Dr. Hulsey noted.

Finally, determine the trigger event and provide patient education as needed to prevent recurrences. Infection, serious illness, trauma, and emotional stress can all lead to the acute diabetic disorder, as can other medications, alcohol, and inappropriate cessation of insulin or reduction of the insulin dosage.

Patients should be made aware of the range of possible precipitating factors. They also should be cognizant of early signs and symptoms that might suggest the need for insulin adjustment, before the situation escalates to an emergency, Dr. Hulsey concluded.

STOWE, VT. — Uncertain triggers, therapeutic controversies, and potentially fatal complications can compromise emergency management of diabetic ketoacidosis, according to Steven M. Hulsey, M.D.

Diabetic ketoacidosis (DKA) is a major, acute metabolic complication of diabetes that requires immediate and intensive care.

Although DKA is not a difficult diagnosis per se—particularly in the context of known type 1 diabetes—evaluation and treatment can be challenging, Dr. Hulsey said at an emergency medicine update sponsored by the University of Vermont.

Diagnosis and management of the severe insulin deficiency that sets the ketoacidotic chain in motion are only half the battle. The other half is identifying the event or condition that precipitated the metabolic disorder and addressing it appropriately to restore normal balance and prevent recurrences.

“Initially, you want to make sure that what is causing the ketoacidosis isn't itself a life-threatening condition, such as myocardial infarction or sepsis,” said Dr. Hulsey, noting that in some cases, the “trigger” could pose at least as great a threat as the DKA.

Excessive urination, severe thirst, fruity-smelling breath, abdominal pain, nausea, vomiting, fatigue, breathing difficulties, and mental confusion are among the telltale symptoms of DKA.

Blood glucose levels higher than 250 mg/dL, large quantities of ketones in the urine and plasma, low serum bicarbonate (less than 15 mmol/L), elevated anion gap (more than 16 mmol/L), and a blood pH of less than 7.3 confirm a diagnosis of DKA.

Because there is no clinically significant difference between arterial and venous pH estimates in patients with DKA, “go ahead and get the venous sample upon insertion of the IV for fluid resuscitation,” Dr. Hulsey recommended. “This spares the patient a painful arterial stick later.”

Severe electrolyte disturbances are also characteristic of DKA. The most dangerous of these, total body potassium loss, is difficult to assess, because it is typically not mirrored in serum potassium levels—a factor that must be considered before treatment.

Initial blood potassium levels usually are normal to high, despite substantial total body potassium deficits. This is because the acidosis encourages leakage of intracellular potassium.

Treatment with insulin—a cornerstone of DKA therapy—drives potassium back into the cells, and levels may drop very quickly.

For this reason, frequent blood potassium checks are critical during therapy.

“If serum potassium levels are even just slightly low on the first test, that means that total body potassium is probably critically low and must be replenished before giving the patient insulin,” Dr. Hulsey said. “If potassium levels are normal, total body potassium is probably low and should be replenished [along with insulin infusion].”

The pillars of DKA treatment include efforts to correct life-threatening dehydration, hyperglycemia, ketonemia and acidemia, and electrolyte disturbances. Toward this end, aggressive fluid resuscitation is warranted unless the patient has signs of any condition, such as congestive heart failure, that might be exacerbated by large volumes of intravenous fluids.

A less aggressive approach is also recommended when treating children and adolescents, who are at greater risk for cerebral edema.

It has been suggested, though not proven, that over-aggressive fluid replacement is linked to this rare, often fatal complication. “But most physicians choose to err on the side of underreplacement in kids,” Dr. Hulsey said.

Intravenous insulin is also indicated, although there is ongoing debate about dosing and infusion rates.

In the past, large doses of insulin were recommended early in DKA therapy. Current thinking is that hyperglycemia should be corrected gradually to avoid hypoglycemia, hypokalemia, and cerebral or pulmonary edema, he said. Blood glucose levels should be monitored hourly, and insulin dose should be adjusted accordingly.

There currently is no consensus on the practice of administering an intravenous bolus of regular insulin as a way to jump-start recovery efforts before low-dose infusion.

“In reality, a bolus dose is not needed [before low-dose infusion] to obtain optimal plasma levels, because the time needed to reach normal glycemic levels is the same,” Dr. Hulsey said. “And there is the possibility that a bolus dose may increase the risk for hypokalemia.”

A bolus dose should be considered, however, when a substantial delay in treatment is anticipated, he said.

In such circumstances, it is not unreasonable to administer successive small bolus doses, as long as potassium levels are being monitored.

The use of intravenous bicarbonate to reduce the immediate risks of extremely low pH is also a contentious topic.

The theoretical advantages include a reduction in cardiac irritability, respiratory discomfort, and intravenous chloride load, while the theoretical disadvantages include the possibility of hypokalemia and arrhythmia and exacerbated intracellular and intracerebral acidosis.

“In reality, there are some studies that have shown that giving bicarbonate in DKA doesn't make a difference either way, so it should probably be avoided” Dr. Hulsey said. Bicarbonate should not be used in pediatric patients, because of a possible association with cerebral edema, he said.

As noted, replacing potassium deficits should be included in the DKA management strategy. The dose will vary depending on serum levels, which should be measured regularly so that the rate of replacement can be adjusted as needed, Dr. Hulsey noted.

Finally, determine the trigger event and provide patient education as needed to prevent recurrences. Infection, serious illness, trauma, and emotional stress can all lead to the acute diabetic disorder, as can other medications, alcohol, and inappropriate cessation of insulin or reduction of the insulin dosage.

Patients should be made aware of the range of possible precipitating factors. They also should be cognizant of early signs and symptoms that might suggest the need for insulin adjustment, before the situation escalates to an emergency, Dr. Hulsey concluded.

STOWE, VT. — Uncertain triggers, therapeutic controversies, and potentially fatal complications can compromise emergency management of diabetic ketoacidosis, according to Steven M. Hulsey, M.D.

Diabetic ketoacidosis (DKA) is a major, acute metabolic complication of diabetes that requires immediate and intensive care.

Although DKA is not a difficult diagnosis per se—particularly in the context of known type 1 diabetes—evaluation and treatment can be challenging, Dr. Hulsey said at an emergency medicine update sponsored by the University of Vermont.

Diagnosis and management of the severe insulin deficiency that sets the ketoacidotic chain in motion are only half the battle. The other half is identifying the event or condition that precipitated the metabolic disorder and addressing it appropriately to restore normal balance and prevent recurrences.

“Initially, you want to make sure that what is causing the ketoacidosis isn't itself a life-threatening condition, such as myocardial infarction or sepsis,” said Dr. Hulsey, noting that in some cases, the “trigger” could pose at least as great a threat as the DKA.

Excessive urination, severe thirst, fruity-smelling breath, abdominal pain, nausea, vomiting, fatigue, breathing difficulties, and mental confusion are among the telltale symptoms of DKA.

Blood glucose levels higher than 250 mg/dL, large quantities of ketones in the urine and plasma, low serum bicarbonate (less than 15 mmol/L), elevated anion gap (more than 16 mmol/L), and a blood pH of less than 7.3 confirm a diagnosis of DKA.

Because there is no clinically significant difference between arterial and venous pH estimates in patients with DKA, “go ahead and get the venous sample upon insertion of the IV for fluid resuscitation,” Dr. Hulsey recommended. “This spares the patient a painful arterial stick later.”

Severe electrolyte disturbances are also characteristic of DKA. The most dangerous of these, total body potassium loss, is difficult to assess, because it is typically not mirrored in serum potassium levels—a factor that must be considered before treatment.

Initial blood potassium levels usually are normal to high, despite substantial total body potassium deficits. This is because the acidosis encourages leakage of intracellular potassium.

Treatment with insulin—a cornerstone of DKA therapy—drives potassium back into the cells, and levels may drop very quickly.

For this reason, frequent blood potassium checks are critical during therapy.

“If serum potassium levels are even just slightly low on the first test, that means that total body potassium is probably critically low and must be replenished before giving the patient insulin,” Dr. Hulsey said. “If potassium levels are normal, total body potassium is probably low and should be replenished [along with insulin infusion].”

The pillars of DKA treatment include efforts to correct life-threatening dehydration, hyperglycemia, ketonemia and acidemia, and electrolyte disturbances. Toward this end, aggressive fluid resuscitation is warranted unless the patient has signs of any condition, such as congestive heart failure, that might be exacerbated by large volumes of intravenous fluids.

A less aggressive approach is also recommended when treating children and adolescents, who are at greater risk for cerebral edema.

It has been suggested, though not proven, that over-aggressive fluid replacement is linked to this rare, often fatal complication. “But most physicians choose to err on the side of underreplacement in kids,” Dr. Hulsey said.

Intravenous insulin is also indicated, although there is ongoing debate about dosing and infusion rates.

In the past, large doses of insulin were recommended early in DKA therapy. Current thinking is that hyperglycemia should be corrected gradually to avoid hypoglycemia, hypokalemia, and cerebral or pulmonary edema, he said. Blood glucose levels should be monitored hourly, and insulin dose should be adjusted accordingly.

There currently is no consensus on the practice of administering an intravenous bolus of regular insulin as a way to jump-start recovery efforts before low-dose infusion.

“In reality, a bolus dose is not needed [before low-dose infusion] to obtain optimal plasma levels, because the time needed to reach normal glycemic levels is the same,” Dr. Hulsey said. “And there is the possibility that a bolus dose may increase the risk for hypokalemia.”

A bolus dose should be considered, however, when a substantial delay in treatment is anticipated, he said.

In such circumstances, it is not unreasonable to administer successive small bolus doses, as long as potassium levels are being monitored.

The use of intravenous bicarbonate to reduce the immediate risks of extremely low pH is also a contentious topic.

The theoretical advantages include a reduction in cardiac irritability, respiratory discomfort, and intravenous chloride load, while the theoretical disadvantages include the possibility of hypokalemia and arrhythmia and exacerbated intracellular and intracerebral acidosis.

“In reality, there are some studies that have shown that giving bicarbonate in DKA doesn't make a difference either way, so it should probably be avoided” Dr. Hulsey said. Bicarbonate should not be used in pediatric patients, because of a possible association with cerebral edema, he said.

As noted, replacing potassium deficits should be included in the DKA management strategy. The dose will vary depending on serum levels, which should be measured regularly so that the rate of replacement can be adjusted as needed, Dr. Hulsey noted.

Finally, determine the trigger event and provide patient education as needed to prevent recurrences. Infection, serious illness, trauma, and emotional stress can all lead to the acute diabetic disorder, as can other medications, alcohol, and inappropriate cessation of insulin or reduction of the insulin dosage.

Patients should be made aware of the range of possible precipitating factors. They also should be cognizant of early signs and symptoms that might suggest the need for insulin adjustment, before the situation escalates to an emergency, Dr. Hulsey concluded.

BOSTON — Regular use of an alcohol-based hand sanitizer in the home can reduce the spread of gastrointestinal infections among family members, Thomas J. Sandora, M.D., said at the annual meeting of the Infectious Diseases Society of America.

And the more hand sanitizer used by a given family, the better the chances of reducing the spread of some organisms, according to the findings from the Healthy Hands, Healthy Families Study at Children's Hospital Boston.

Dr. Sandora and his colleagues provided 155 families that had at least one child in day care with hand sanitizer and hand hygiene educational materials. A control group of 137 day-care families with similar demographics was given materials about basic nutrition only.

The investigators tracked all of the families for 5 months, using biweekly phone calls to inquire about symptoms of respiratory and gastrointestinal illness. The primary outcome measures were rates of secondary transmission of both types of illnesses per susceptible person-year.

During the observation period, 28 of 252 gastrointestinal illnesses recorded were classified as secondary transmissions (time of onset 2 to 7 days after onset in another family member), as were 443 of 1,802 respiratory illnesses. The use of hand sanitizer reduced the overall secondary transmission of gastrointestinal infections by 59%.

Alcohol-based hand sanitizer removes surface germs on the skin. “Alcohol does not contain antibiotics, and you don't develop resistance to it,” Dr. Sandora noted.

GOJO Industries—the manufacturer of the hand sanitizer gel used in the study—funded the research study. Dr. Sandora reported having no financial interests in the company.

BOSTON — Regular use of an alcohol-based hand sanitizer in the home can reduce the spread of gastrointestinal infections among family members, Thomas J. Sandora, M.D., said at the annual meeting of the Infectious Diseases Society of America.

And the more hand sanitizer used by a given family, the better the chances of reducing the spread of some organisms, according to the findings from the Healthy Hands, Healthy Families Study at Children's Hospital Boston.

Dr. Sandora and his colleagues provided 155 families that had at least one child in day care with hand sanitizer and hand hygiene educational materials. A control group of 137 day-care families with similar demographics was given materials about basic nutrition only.

The investigators tracked all of the families for 5 months, using biweekly phone calls to inquire about symptoms of respiratory and gastrointestinal illness. The primary outcome measures were rates of secondary transmission of both types of illnesses per susceptible person-year.

During the observation period, 28 of 252 gastrointestinal illnesses recorded were classified as secondary transmissions (time of onset 2 to 7 days after onset in another family member), as were 443 of 1,802 respiratory illnesses. The use of hand sanitizer reduced the overall secondary transmission of gastrointestinal infections by 59%.

Alcohol-based hand sanitizer removes surface germs on the skin. “Alcohol does not contain antibiotics, and you don't develop resistance to it,” Dr. Sandora noted.

GOJO Industries—the manufacturer of the hand sanitizer gel used in the study—funded the research study. Dr. Sandora reported having no financial interests in the company.

BOSTON — Regular use of an alcohol-based hand sanitizer in the home can reduce the spread of gastrointestinal infections among family members, Thomas J. Sandora, M.D., said at the annual meeting of the Infectious Diseases Society of America.

And the more hand sanitizer used by a given family, the better the chances of reducing the spread of some organisms, according to the findings from the Healthy Hands, Healthy Families Study at Children's Hospital Boston.

Dr. Sandora and his colleagues provided 155 families that had at least one child in day care with hand sanitizer and hand hygiene educational materials. A control group of 137 day-care families with similar demographics was given materials about basic nutrition only.

The investigators tracked all of the families for 5 months, using biweekly phone calls to inquire about symptoms of respiratory and gastrointestinal illness. The primary outcome measures were rates of secondary transmission of both types of illnesses per susceptible person-year.

During the observation period, 28 of 252 gastrointestinal illnesses recorded were classified as secondary transmissions (time of onset 2 to 7 days after onset in another family member), as were 443 of 1,802 respiratory illnesses. The use of hand sanitizer reduced the overall secondary transmission of gastrointestinal infections by 59%.

Alcohol-based hand sanitizer removes surface germs on the skin. “Alcohol does not contain antibiotics, and you don't develop resistance to it,” Dr. Sandora noted.

GOJO Industries—the manufacturer of the hand sanitizer gel used in the study—funded the research study. Dr. Sandora reported having no financial interests in the company.

HARROGATE, ENGLAND — A woman's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable, he said.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjustment for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking, and umbilical cord phosphate, calcium, and albumin levels did not.

Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status, he said.

HARROGATE, ENGLAND — A woman's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable, he said.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjustment for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking, and umbilical cord phosphate, calcium, and albumin levels did not.

Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status, he said.

HARROGATE, ENGLAND — A woman's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable, he said.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjustment for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking, and umbilical cord phosphate, calcium, and albumin levels did not.

Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status, he said.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old. The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation. None used hormonal contraception or hormone therapy.

The investigators grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer, Dr. Repse-Fokter said. “In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted. The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density. The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old. The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation. None used hormonal contraception or hormone therapy.

The investigators grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer, Dr. Repse-Fokter said. “In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted. The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density. The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old. The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation. None used hormonal contraception or hormone therapy.

The investigators grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer, Dr. Repse-Fokter said. “In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted. The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density. The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women who are at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old.

The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation.

None of the women used hormonal contraception or hormone therapy, Dr. Repse-Fokter said.

The investigator and her associates grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer.

“In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted.

The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density, Dr. Repse-Fokter said.

The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The findings of a correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women who are at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old.

The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation.

None of the women used hormonal contraception or hormone therapy, Dr. Repse-Fokter said.

The investigator and her associates grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer.

“In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted.

The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density, Dr. Repse-Fokter said.

The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The findings of a correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — Women whose Pap smears reveal atrophic cell patterns may be at greater risk for osteopenia and osteoporosis than women whose smears show mature cell patterns, a study has shown.

The findings suggest that routine Pap testing could be a useful and inexpensive screening tool for identifying women who are at risk for the degenerative bone disorders, Alenka Repse-Fokter, M.D., reported in a poster presentation at the annual conference of the National Osteoporosis Society.

Given limited medical resources, the ability to use an already existing and widely performed screening protocol to help identify women with osteoporosis “would be highly appreciated,” she said.

Dr. Repse-Fokter and colleagues at Celje (Slovenia) General Hospital assessed the Pap smear results and dual-energy x-ray absorptiometry (DXA) bone density measurements of 66 women between 46 and 67 years old.

The women had received the Pap smears for routine cervical cancer screening and were invited to undergo bone mineral density measurement as part of the investigation.

None of the women used hormonal contraception or hormone therapy, Dr. Repse-Fokter said.

The investigator and her associates grouped the smears into atrophic and mature cell patterns, which can be easily recognized during the screening for cervical dysplasia or cancer.

“In routine light microscopy, atrophic cells appear much smaller than cells in mature smear patterns,” she noted.

The smear patterns were then compared with the patients' T values measured by DXA on the femoral neck and lumbar spine.

Overall, the T scores were significantly lower in the atrophic smear group. Of the 33 women with atrophic smears, 13 had osteopenia and 15 had osteoporosis. Among the 33 women whose smears showed mature cell patterns, 9 had osteopenia and 24 had normal bone density, Dr. Repse-Fokter said.

The sensitivity, specificity, and positive predictive value of the findings were, respectively, 76%, 83%, and 85%.

The findings of a correlation between smear patterns and degenerative bone disease support the investigators' findings from a previous study that revealed a highly significant association between atrophic smear patterns and low bone mineral density.

“This means that a significant number of women with low bone mineral density who are at high risk [for osteoporotic disease] could be identified in parallel with routine Pap testing for cervical cancer screening without added costs,” Dr. Repse-Fokter said.

Although further studies on larger populations are needed, “we strongly suggest that women with atrophic Pap smear patterns be closely followed as recommended by the American National Osteoporosis Foundation,” according to Dr. Repse-Fokter and her colleagues.

HARROGATE, ENGLAND — A mother's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjusting for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four-fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking and umbilical cord phosphate, calcium, and albumin levels did not. Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status. The findings are especially timely, given that vitamin D deficiency is re-emerging as a significant problem among pregnant women and their infants, particularly among groups with dark skin or low skin exposure to sunlight, Dr. Harvey said. Checking a mother's vitamin D status and recommending sufficient supplementation for women who are deficient are simple steps “that could potentially reduce fractures in future generations,” he said.

HARROGATE, ENGLAND — A mother's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjusting for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four-fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking and umbilical cord phosphate, calcium, and albumin levels did not. Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status. The findings are especially timely, given that vitamin D deficiency is re-emerging as a significant problem among pregnant women and their infants, particularly among groups with dark skin or low skin exposure to sunlight, Dr. Harvey said. Checking a mother's vitamin D status and recommending sufficient supplementation for women who are deficient are simple steps “that could potentially reduce fractures in future generations,” he said.

HARROGATE, ENGLAND — A mother's vitamin D status in late pregnancy is predictive of her offspring's lumbar spine volumetric bone density at age 9, a prospective study has shown.

The findings add to the growing body of evidence confirming that a woman's diet while pregnant can influence her child's later bone mass, said Nicholas W. Harvey, B.Chir.

The results of the population-based investigation also point to the potential efficacy of preventive measures to protect children's bone health, Dr. Harvey said in a presentation at the annual conference of the National Osteoporosis Society. “Vitamin D supplementation in pregnant women who are deficient may optimize peak accrual of bone mineral in their offspring,” he stated.

The investigation included 210 offspring of mothers enrolled in a larger cohort study of maternal nutrition and fetal development conducted by Dr. Harvey and his colleagues at the MRC environmental epidemiology unit of the University of Southampton (England). The mothers completed a questionnaire regarding their diet and lifestyle beginning from early pregnancy.

Anthropometric measures were recorded, including mid-upper arm circumference, which is a potential indicator of maternal nutritional status. The mothers gave venous blood samples in late pregnancy for the measurement of 25-hydroxyvitamin D levels and other nutrients. Concentrated umbilical cord blood was collected at birth to measure calcium, albumin, and phosphate.

The investigators recorded the size and weight of the offspring at birth. When the children reached age 9 years, they underwent dual-energy x-ray absorptiometry (DXA) for bone mass measurement. Because bone mineral density measured by DXA represents the areal density (grams per square centimeter) rather than the volumetric density (grams per cubic centimeter) of bone, the investigators generated mathematical estimates of volumetric bone density from the DXA measurements of bone mineral content and bone area.

“When studying bone mineral density during growth, the differences [between volumetric and areal BMD] have to be taken into consideration,” Dr. Harvey explained. As bones grow, the volume increases at a faster rate than the area, so the areal bone density will increase even if the volumetric density remains stable.

At 9 years, the boys in the study group (112) were significantly taller than the girls, and had higher age-adjusted lumbar spine bone mineral content and bone area but lower volumetric bone mineral density. After adjusting for child age and gender, maternal vitamin D was positively correlated with childhood volumetric BMD. “There was a threshold in the relationship, such that mothers in the lowest fifth of the [vitamin D] distribution had children with significantly lower volumetric bone mineral density at age 9 than those in the remaining four-fifths,” Dr. Harvey said.

Maternal mid-upper arm circumference and vitamin D supplementation in late pregnancy both had significant positive associations with volumetric BMD, while social class, maternal smoking and umbilical cord phosphate, calcium, and albumin levels did not. Calcium from the cord blood was predictive of increased bone mass, but not volumetric BMD, Dr. Harvey noted.

In a multivariate model, both maternal mid-upper arm circumference and low serum vitamin D remained significant predictors of childhood volumetric BMD status. The findings are especially timely, given that vitamin D deficiency is re-emerging as a significant problem among pregnant women and their infants, particularly among groups with dark skin or low skin exposure to sunlight, Dr. Harvey said. Checking a mother's vitamin D status and recommending sufficient supplementation for women who are deficient are simple steps “that could potentially reduce fractures in future generations,” he said.