Miriam E. Tucker

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they do not have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting that was held by telephone in response to the multistate outbreak of mumps that began in Iowa late last year.

Between Jan. 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (five or more outbreak-associated cases) with ongoing local transmission or clusters of cases. Three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, composing 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect. For 120 (5%) cases, classification was unknown (MMWR 2006:55[Dispatch];1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at age 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they do not have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting that was held by telephone in response to the multistate outbreak of mumps that began in Iowa late last year.

Between Jan. 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (five or more outbreak-associated cases) with ongoing local transmission or clusters of cases. Three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, composing 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect. For 120 (5%) cases, classification was unknown (MMWR 2006:55[Dispatch];1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at age 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they do not have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting that was held by telephone in response to the multistate outbreak of mumps that began in Iowa late last year.

Between Jan. 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (five or more outbreak-associated cases) with ongoing local transmission or clusters of cases. Three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, composing 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect. For 120 (5%) cases, classification was unknown (MMWR 2006:55[Dispatch];1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at age 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

PHILADELPHIA — Drug interactions involving warfarin are among the most dangerous that occur commonly in clinical practice, Dr. Douglas S. Paauw said at the annual meeting of the American College of Physicians.

As many as one-third of all hospitalizations in the United States are associated with drug interactions or side effects, and warfarin is one of the main culprits. “If you look statistically at what are the drug interactions that kill people, warfarin interactions are at the top of the list,” noted Dr. Paauw, professor of medicine at the University of Washington, Seattle.

With binders such as cholestyramine, for example, the interference actually happens twice. Cholestyramine directly binds the anticoagulant and decreases its absorption when the two drugs are taken together. In addition, the enterohepatic circulation of warfarin—in which it is excreted in the bile and then reabsorbed—results in a “second pass” anticoagulant effect and a second interaction with the binder, which can lead to a further decrease in warfarin effectiveness. This secondary effect can't be prevented by separating the doses.

If possible, try to avoid using binders in patients taking warfarin, Dr. Paauw advised. If both must be taken, be sure to separate them so that the warfarin is taken at night and the binder taken in the morning and perhaps in the afternoon. Very close monitoring of the international normalized ratio (INR) is essential when initiating the binder. “But if you can get away from [using the two concurrently], that's a safer way to go,” he said.

Interactions between antibiotics and warfarin are also quite common, with trimethoprim-sulfamethoxazole (TMP-SMX) having the greatest potential to cause a severe interaction. Other antibiotics that can lead to overanticoagulation when taken with warfarin include erythromycin, amiodarone, ketoconazole/fluconazole (in high doses), itraconazole, and metronidazole. None, however, is as powerful as the interaction with TMP-SMX, because it has a shorter half-life than other antimicrobials and therefore the effect can occur within 2–3 days. With the others, there is usually enough time for the increase in INR to be picked up and treated before it gets out of hand, Dr. Paauw noted.

Other antibiotics that may increase the INR in some, but not all, anticoagulated patients include quinolones, omeprazole, clarithromycin, and azithromycin. These drugs are more likely to cause problems in elderly patients and in those who are taking many concurrent medications.

In a retrospective study involving 104 patients on stable warfarin therapy, INR increased by 0.51 with azithromycin, 0.85 with levofloxacin, and 1.76 with TMP-SMX, compared with an insignificant drop of 0.15 with terazocin, which was used as the control. The incidence of overanticoagulation was 5% with terazocin, 31% with azithromycin, 33% with levofloxacin, and 69% with TMP-SMX (J. Gen. Intern. Med. 2005;20:653–6).

Over-the-counter medications might also interact with warfarin. Acetaminophen, which is often recommended for pain relief to patients taking warfarin specifically because it doesn't increase the risk of gastrointestinal bleeding, can actually increase bleeding by interacting with the anticoagulant. In one study, acetaminophen doses of greater than 9,100 mg/week led to a 10-fold risk of having an INR greater than 6 (JAMA 1998;279:657–62). That amount of acetaminophen is the equivalent of just 2–3 extra-strength Tylenol tablets a day, Dr. Paauw pointed out.

In a randomized, double-blind crossover trial of patients on daily warfarin, adding 4 g/day of acetaminophen (the upper limit recommended on the bottle) resulted in an INR 1.75 times greater than that which occurred with placebo.

Still, acetaminophen is much safer for anticoagulated patients than are nonsteroidal drugs and shouldn't cause a problem in a patient who takes only a couple of tablets every few weeks for occasional pain. For patients with chronic pain who need daily analgesia, INR should be measured within 4–5 days after starting the analgesic, he advised.

Alternative treatments also can cause problems with warfarin. Garlic, ginger, ginkgo biloba, feverfew (used for migraines), and the herb dong quai (for menstrual cramps) can all increase the anticoagulant effect, while ginseng can decrease it. Ginkgo, used to treat a variety of vascular problems, has its own anticoagulant effect, and there have been case reports of spontaneous subdural hematomas in patients taking it. No data are available to quantify the risk, but “it makes sense not to take it when you're anticoagulated,” Dr. Paauw said.

St. John's wort, a metabolically active supplement used to treat depression, can both increase and decrease warfarin's anticoagulant effect and therefore should be avoided in patients on warfarin, he recommended.

Dr. Paauw is on the speakers' bureau for Pfizer Inc.

PHILADELPHIA — Drug interactions involving warfarin are among the most dangerous that occur commonly in clinical practice, Dr. Douglas S. Paauw said at the annual meeting of the American College of Physicians.

As many as one-third of all hospitalizations in the United States are associated with drug interactions or side effects, and warfarin is one of the main culprits. “If you look statistically at what are the drug interactions that kill people, warfarin interactions are at the top of the list,” noted Dr. Paauw, professor of medicine at the University of Washington, Seattle.

With binders such as cholestyramine, for example, the interference actually happens twice. Cholestyramine directly binds the anticoagulant and decreases its absorption when the two drugs are taken together. In addition, the enterohepatic circulation of warfarin—in which it is excreted in the bile and then reabsorbed—results in a “second pass” anticoagulant effect and a second interaction with the binder, which can lead to a further decrease in warfarin effectiveness. This secondary effect can't be prevented by separating the doses.

If possible, try to avoid using binders in patients taking warfarin, Dr. Paauw advised. If both must be taken, be sure to separate them so that the warfarin is taken at night and the binder taken in the morning and perhaps in the afternoon. Very close monitoring of the international normalized ratio (INR) is essential when initiating the binder. “But if you can get away from [using the two concurrently], that's a safer way to go,” he said.

Interactions between antibiotics and warfarin are also quite common, with trimethoprim-sulfamethoxazole (TMP-SMX) having the greatest potential to cause a severe interaction. Other antibiotics that can lead to overanticoagulation when taken with warfarin include erythromycin, amiodarone, ketoconazole/fluconazole (in high doses), itraconazole, and metronidazole. None, however, is as powerful as the interaction with TMP-SMX, because it has a shorter half-life than other antimicrobials and therefore the effect can occur within 2–3 days. With the others, there is usually enough time for the increase in INR to be picked up and treated before it gets out of hand, Dr. Paauw noted.

Other antibiotics that may increase the INR in some, but not all, anticoagulated patients include quinolones, omeprazole, clarithromycin, and azithromycin. These drugs are more likely to cause problems in elderly patients and in those who are taking many concurrent medications.

In a retrospective study involving 104 patients on stable warfarin therapy, INR increased by 0.51 with azithromycin, 0.85 with levofloxacin, and 1.76 with TMP-SMX, compared with an insignificant drop of 0.15 with terazocin, which was used as the control. The incidence of overanticoagulation was 5% with terazocin, 31% with azithromycin, 33% with levofloxacin, and 69% with TMP-SMX (J. Gen. Intern. Med. 2005;20:653–6).

Over-the-counter medications might also interact with warfarin. Acetaminophen, which is often recommended for pain relief to patients taking warfarin specifically because it doesn't increase the risk of gastrointestinal bleeding, can actually increase bleeding by interacting with the anticoagulant. In one study, acetaminophen doses of greater than 9,100 mg/week led to a 10-fold risk of having an INR greater than 6 (JAMA 1998;279:657–62). That amount of acetaminophen is the equivalent of just 2–3 extra-strength Tylenol tablets a day, Dr. Paauw pointed out.

In a randomized, double-blind crossover trial of patients on daily warfarin, adding 4 g/day of acetaminophen (the upper limit recommended on the bottle) resulted in an INR 1.75 times greater than that which occurred with placebo.

Still, acetaminophen is much safer for anticoagulated patients than are nonsteroidal drugs and shouldn't cause a problem in a patient who takes only a couple of tablets every few weeks for occasional pain. For patients with chronic pain who need daily analgesia, INR should be measured within 4–5 days after starting the analgesic, he advised.

Alternative treatments also can cause problems with warfarin. Garlic, ginger, ginkgo biloba, feverfew (used for migraines), and the herb dong quai (for menstrual cramps) can all increase the anticoagulant effect, while ginseng can decrease it. Ginkgo, used to treat a variety of vascular problems, has its own anticoagulant effect, and there have been case reports of spontaneous subdural hematomas in patients taking it. No data are available to quantify the risk, but “it makes sense not to take it when you're anticoagulated,” Dr. Paauw said.

St. John's wort, a metabolically active supplement used to treat depression, can both increase and decrease warfarin's anticoagulant effect and therefore should be avoided in patients on warfarin, he recommended.

Dr. Paauw is on the speakers' bureau for Pfizer Inc.

PHILADELPHIA — Drug interactions involving warfarin are among the most dangerous that occur commonly in clinical practice, Dr. Douglas S. Paauw said at the annual meeting of the American College of Physicians.

As many as one-third of all hospitalizations in the United States are associated with drug interactions or side effects, and warfarin is one of the main culprits. “If you look statistically at what are the drug interactions that kill people, warfarin interactions are at the top of the list,” noted Dr. Paauw, professor of medicine at the University of Washington, Seattle.

With binders such as cholestyramine, for example, the interference actually happens twice. Cholestyramine directly binds the anticoagulant and decreases its absorption when the two drugs are taken together. In addition, the enterohepatic circulation of warfarin—in which it is excreted in the bile and then reabsorbed—results in a “second pass” anticoagulant effect and a second interaction with the binder, which can lead to a further decrease in warfarin effectiveness. This secondary effect can't be prevented by separating the doses.

If possible, try to avoid using binders in patients taking warfarin, Dr. Paauw advised. If both must be taken, be sure to separate them so that the warfarin is taken at night and the binder taken in the morning and perhaps in the afternoon. Very close monitoring of the international normalized ratio (INR) is essential when initiating the binder. “But if you can get away from [using the two concurrently], that's a safer way to go,” he said.

Interactions between antibiotics and warfarin are also quite common, with trimethoprim-sulfamethoxazole (TMP-SMX) having the greatest potential to cause a severe interaction. Other antibiotics that can lead to overanticoagulation when taken with warfarin include erythromycin, amiodarone, ketoconazole/fluconazole (in high doses), itraconazole, and metronidazole. None, however, is as powerful as the interaction with TMP-SMX, because it has a shorter half-life than other antimicrobials and therefore the effect can occur within 2–3 days. With the others, there is usually enough time for the increase in INR to be picked up and treated before it gets out of hand, Dr. Paauw noted.

Other antibiotics that may increase the INR in some, but not all, anticoagulated patients include quinolones, omeprazole, clarithromycin, and azithromycin. These drugs are more likely to cause problems in elderly patients and in those who are taking many concurrent medications.

In a retrospective study involving 104 patients on stable warfarin therapy, INR increased by 0.51 with azithromycin, 0.85 with levofloxacin, and 1.76 with TMP-SMX, compared with an insignificant drop of 0.15 with terazocin, which was used as the control. The incidence of overanticoagulation was 5% with terazocin, 31% with azithromycin, 33% with levofloxacin, and 69% with TMP-SMX (J. Gen. Intern. Med. 2005;20:653–6).

Over-the-counter medications might also interact with warfarin. Acetaminophen, which is often recommended for pain relief to patients taking warfarin specifically because it doesn't increase the risk of gastrointestinal bleeding, can actually increase bleeding by interacting with the anticoagulant. In one study, acetaminophen doses of greater than 9,100 mg/week led to a 10-fold risk of having an INR greater than 6 (JAMA 1998;279:657–62). That amount of acetaminophen is the equivalent of just 2–3 extra-strength Tylenol tablets a day, Dr. Paauw pointed out.

In a randomized, double-blind crossover trial of patients on daily warfarin, adding 4 g/day of acetaminophen (the upper limit recommended on the bottle) resulted in an INR 1.75 times greater than that which occurred with placebo.

Still, acetaminophen is much safer for anticoagulated patients than are nonsteroidal drugs and shouldn't cause a problem in a patient who takes only a couple of tablets every few weeks for occasional pain. For patients with chronic pain who need daily analgesia, INR should be measured within 4–5 days after starting the analgesic, he advised.

Alternative treatments also can cause problems with warfarin. Garlic, ginger, ginkgo biloba, feverfew (used for migraines), and the herb dong quai (for menstrual cramps) can all increase the anticoagulant effect, while ginseng can decrease it. Ginkgo, used to treat a variety of vascular problems, has its own anticoagulant effect, and there have been case reports of spontaneous subdural hematomas in patients taking it. No data are available to quantify the risk, but “it makes sense not to take it when you're anticoagulated,” Dr. Paauw said.

St. John's wort, a metabolically active supplement used to treat depression, can both increase and decrease warfarin's anticoagulant effect and therefore should be avoided in patients on warfarin, he recommended.

Dr. Paauw is on the speakers' bureau for Pfizer Inc.

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they don't have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting held by telephone in response to the current multistate mumps outbreak that began in Iowa late last year.

Between January 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (5 or more outbreak-associated cases) with ongoing local transmission or clusters of cases; three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, comprising 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect; for 120 (5%) cases, classification was unknown (MMWR 2006;55[Dispatch]:1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at ages 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity (such as birth before 1957, documentation of physician-diagnosed mumps, or laboratory evidence of immunity) remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose, the minimum recommended interval between two MMR vaccine doses. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they don't have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting held by telephone in response to the current multistate mumps outbreak that began in Iowa late last year.

Between January 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (5 or more outbreak-associated cases) with ongoing local transmission or clusters of cases; three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, comprising 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect; for 120 (5%) cases, classification was unknown (MMWR 2006;55[Dispatch]:1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at ages 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity (such as birth before 1957, documentation of physician-diagnosed mumps, or laboratory evidence of immunity) remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose, the minimum recommended interval between two MMR vaccine doses. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

All health care workers should receive two doses of the measles-mumps-rubella vaccine if they don't have evidence of immunity, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted during a special meeting held by telephone in response to the current multistate mumps outbreak that began in Iowa late last year.

Between January 1 and May 2, 11 states reported 2,597 cases of mumps. Eight states (Illinois, Iowa, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota, and Wisconsin) reported mumps outbreaks (5 or more outbreak-associated cases) with ongoing local transmission or clusters of cases; three states (Colorado, Minnesota, and Mississippi) reported cases associated with travel from an outbreak state.

The majority of mumps cases (1,487, comprising 57%) were reported from Iowa; states with the next highest case totals were Kansas (371), Illinois (224), Nebraska (201), and Wisconsin (176). Of the 2,597 cases reported overall, 1,275 (49%) were classified as confirmed, 915 (35%) as probable, and 287 (11%) as suspect; for 120 (5%) cases, classification was unknown (MMWR 2006;55[Dispatch]:1–5).

To prevent mumps, ACIP has long recommended a two-dose MMR vaccination series for all children, with the first dose administered at ages 12–15 months and the second dose at ages 4–6 years. Two doses of MMR vaccine are recommended for school and college entry unless the student has other evidence of immunity.

In the specially convened meeting—the results of which are considered interim—the committee redefined evidence of immunity to mumps through vaccination as follows: One dose of a live mumps virus vaccine for preschool children and adults not at high risk; two doses for children in grades kindergarten through 12 and adults at high risk (such as persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Other criteria for evidence of immunity (such as birth before 1957, documentation of physician-diagnosed mumps, or laboratory evidence of immunity) remain unchanged.

Furthermore, health care facilities should consider recommending one dose of MMR vaccine to unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity.

During an outbreak and depending on the epidemiology of the outbreak (the age groups and/or institutions involved), a second dose of vaccine should be considered for adults and for children aged 1–4 years who have received one dose. The second dose should be administered as early as 28 days after the first dose, the minimum recommended interval between two MMR vaccine doses. In addition, during an outbreak, health care facilities should strongly consider recommending two doses of MMR vaccine to unvaccinated workers born before 1957 who do not have other evidence of mumps immunity.

PHILADELPHIA — The American College of Physicians' 3-year diabetes initiative is off and running, Dr. Vincenza Snow said at a press briefing during the college's annual meeting.

The program, announced last year, is funded by a $9.27 million unrestricted educational grant from Denmark-based insulin manufacturer Novo Nordisk. The initiative aims to “increase awareness of the gap between current practice and acceptable standards of diabetes care, provide educational interventions to improve diabetes care, increase physician awareness of what constitutes high-quality, evidence-based care, and recognize medical practices that improve their diabetes care,” according to an ACP statement.

To help meet those educational goals, the ACP meeting included 16 educational sessions on diabetes during 23 separate time slots (some were offered twice), compared with 8 topics in 16 sessions offered last year, said Dr. Snow, director of clinical programs and quality of care at ACP, and clinical director of the diabetes initiative.

Another element of the initiative, the new patient guide called “Living with Diabetes,” was developed under the guidance of experts in both diabetes and health literacy and a psychologist, based on input from patients, physicians, nurse-educators, pharmacists, and other members of the diabetes “team.” Written in English and Spanish, the guide is “conversational and warm. It leaves patients feeling confident and encouraged,” said Terry Davis, Ph.D., the psychologist who worked on the guide.

The guide organizes the information based on what's most important to patients. For example, the chapter on food is the longest and is placed at the front, explained Dr. Davis, professor of medicine and pediatrics at Louisiana State University Health Sciences Center, Shreveport.

Another aspect of the initiative, “Closing the Gap,” held its first training session at this year's meeting. Nineteen practices from across the country each sent two staff members to participate in intensive quality-improvement training, which they will take back to their practices and use to train their office staff.

Dr. Michael A. Weisz has made ACP's overall “Closing the Gap” program—aimed at training teams of health care providers to improve quality of care for patients with a variety of chronic conditions—central to his tenure as ACP governor for Oklahoma. Five Oklahoma physician practices attended the “Closing the Gap” workshops this year.

“I've been in practice now 18 years, and this is a totally different way of taking care of patients. Rather than focusing on single [patient evaluations], it's a way of focusing on diseases and changing the system of how we do that,” said Dr. Weisz, vice chairman of internal medicine and residency program director of the University of Oklahoma in Tulsa.

Physicians shouldn't look at quality improvement as a seismic shift, Dr. Weisz advised. “The idea is to go back and make small changes and see what happens. If something doesn't work, you can make [another] quick change.”

PHILADELPHIA — The American College of Physicians' 3-year diabetes initiative is off and running, Dr. Vincenza Snow said at a press briefing during the college's annual meeting.

The program, announced last year, is funded by a $9.27 million unrestricted educational grant from Denmark-based insulin manufacturer Novo Nordisk. The initiative aims to “increase awareness of the gap between current practice and acceptable standards of diabetes care, provide educational interventions to improve diabetes care, increase physician awareness of what constitutes high-quality, evidence-based care, and recognize medical practices that improve their diabetes care,” according to an ACP statement.

To help meet those educational goals, the ACP meeting included 16 educational sessions on diabetes during 23 separate time slots (some were offered twice), compared with 8 topics in 16 sessions offered last year, said Dr. Snow, director of clinical programs and quality of care at ACP, and clinical director of the diabetes initiative.

Another element of the initiative, the new patient guide called “Living with Diabetes,” was developed under the guidance of experts in both diabetes and health literacy and a psychologist, based on input from patients, physicians, nurse-educators, pharmacists, and other members of the diabetes “team.” Written in English and Spanish, the guide is “conversational and warm. It leaves patients feeling confident and encouraged,” said Terry Davis, Ph.D., the psychologist who worked on the guide.

The guide organizes the information based on what's most important to patients. For example, the chapter on food is the longest and is placed at the front, explained Dr. Davis, professor of medicine and pediatrics at Louisiana State University Health Sciences Center, Shreveport.

Another aspect of the initiative, “Closing the Gap,” held its first training session at this year's meeting. Nineteen practices from across the country each sent two staff members to participate in intensive quality-improvement training, which they will take back to their practices and use to train their office staff.

Dr. Michael A. Weisz has made ACP's overall “Closing the Gap” program—aimed at training teams of health care providers to improve quality of care for patients with a variety of chronic conditions—central to his tenure as ACP governor for Oklahoma. Five Oklahoma physician practices attended the “Closing the Gap” workshops this year.

“I've been in practice now 18 years, and this is a totally different way of taking care of patients. Rather than focusing on single [patient evaluations], it's a way of focusing on diseases and changing the system of how we do that,” said Dr. Weisz, vice chairman of internal medicine and residency program director of the University of Oklahoma in Tulsa.

Physicians shouldn't look at quality improvement as a seismic shift, Dr. Weisz advised. “The idea is to go back and make small changes and see what happens. If something doesn't work, you can make [another] quick change.”

PHILADELPHIA — The American College of Physicians' 3-year diabetes initiative is off and running, Dr. Vincenza Snow said at a press briefing during the college's annual meeting.

The program, announced last year, is funded by a $9.27 million unrestricted educational grant from Denmark-based insulin manufacturer Novo Nordisk. The initiative aims to “increase awareness of the gap between current practice and acceptable standards of diabetes care, provide educational interventions to improve diabetes care, increase physician awareness of what constitutes high-quality, evidence-based care, and recognize medical practices that improve their diabetes care,” according to an ACP statement.

To help meet those educational goals, the ACP meeting included 16 educational sessions on diabetes during 23 separate time slots (some were offered twice), compared with 8 topics in 16 sessions offered last year, said Dr. Snow, director of clinical programs and quality of care at ACP, and clinical director of the diabetes initiative.

Another element of the initiative, the new patient guide called “Living with Diabetes,” was developed under the guidance of experts in both diabetes and health literacy and a psychologist, based on input from patients, physicians, nurse-educators, pharmacists, and other members of the diabetes “team.” Written in English and Spanish, the guide is “conversational and warm. It leaves patients feeling confident and encouraged,” said Terry Davis, Ph.D., the psychologist who worked on the guide.

The guide organizes the information based on what's most important to patients. For example, the chapter on food is the longest and is placed at the front, explained Dr. Davis, professor of medicine and pediatrics at Louisiana State University Health Sciences Center, Shreveport.

Another aspect of the initiative, “Closing the Gap,” held its first training session at this year's meeting. Nineteen practices from across the country each sent two staff members to participate in intensive quality-improvement training, which they will take back to their practices and use to train their office staff.

Dr. Michael A. Weisz has made ACP's overall “Closing the Gap” program—aimed at training teams of health care providers to improve quality of care for patients with a variety of chronic conditions—central to his tenure as ACP governor for Oklahoma. Five Oklahoma physician practices attended the “Closing the Gap” workshops this year.

“I've been in practice now 18 years, and this is a totally different way of taking care of patients. Rather than focusing on single [patient evaluations], it's a way of focusing on diseases and changing the system of how we do that,” said Dr. Weisz, vice chairman of internal medicine and residency program director of the University of Oklahoma in Tulsa.

Physicians shouldn't look at quality improvement as a seismic shift, Dr. Weisz advised. “The idea is to go back and make small changes and see what happens. If something doesn't work, you can make [another] quick change.”

PHILADELPHIA — Nonalcoholic fatty liver disease is emerging as a major health burden in the United States, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Often associated with obesity and underlying insulin resistance, nonalcoholic fatty liver disease (NAFLD) is believed to affect as much as 20%–30% of the U.S. population, said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

There is some debate about the amount of alcohol ingestion permitted to make the distinction between alcoholic steatosis and NAFLD, which is defined as increased liver weight by 5%–10% as a result of fat accumulation (steatosis), in the absence of excessive alcohol consumption.

Most experts agree, however, that overall alcohol consumption of less than 20 g per day is well below that which would be associated with significant alcoholic liver disease, noted Dr. Reddy, who is also medical director of liver transplantation at the university.

Classification of NAFLD falls into four types: Type 1 (fatty liver alone) and type 2 (fat accumulation and lobular inflammation) are considered to be NAFLD alone. The more serious types 3 (fat accumulation and ballooning degeneration) and 4 (fat accumulation, ballooning degeneration, and either Mallory hyaline and/or fibrosis) are characterized as nonalcoholic steatohepatitis (NASH).

“There is a tendency to use the term NASH loosely in everyone who has nonalcoholic fatty liver disease. You should use the general term NAFLD and reserve NASH only for those who have histologic evidence of steatohepatitis,” Dr. Reddy advised.

Overall, about 10% of patients with NAFLD have NASH. Limited data on the natural history of these conditions suggest that about 15%–20% of patients with steatosis will progress to steatohepatitis at some point. Of those, smaller numbers will go on to develop fibrosis, cirrhosis, and hepatocellular carcinoma. The exact percentages have varied widely in different studies.

Factors that predict progression from NAFLD to NASH include age greater than 45 years, type 2 diabetes, body mass index greater than 35 kg/m

Data pertaining to treatment of NAFLD are also limited, but weight management is considered a major priority for all patients because of proven benefits in cardiovascular risk profile.

Overall, about 10% of patients with nonalcoholic fatty liver disease have nonalcoholic steatohepatitis. DR. REDDY

PHILADELPHIA — Nonalcoholic fatty liver disease is emerging as a major health burden in the United States, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Often associated with obesity and underlying insulin resistance, nonalcoholic fatty liver disease (NAFLD) is believed to affect as much as 20%–30% of the U.S. population, said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

There is some debate about the amount of alcohol ingestion permitted to make the distinction between alcoholic steatosis and NAFLD, which is defined as increased liver weight by 5%–10% as a result of fat accumulation (steatosis), in the absence of excessive alcohol consumption.

Most experts agree, however, that overall alcohol consumption of less than 20 g per day is well below that which would be associated with significant alcoholic liver disease, noted Dr. Reddy, who is also medical director of liver transplantation at the university.

Classification of NAFLD falls into four types: Type 1 (fatty liver alone) and type 2 (fat accumulation and lobular inflammation) are considered to be NAFLD alone. The more serious types 3 (fat accumulation and ballooning degeneration) and 4 (fat accumulation, ballooning degeneration, and either Mallory hyaline and/or fibrosis) are characterized as nonalcoholic steatohepatitis (NASH).

“There is a tendency to use the term NASH loosely in everyone who has nonalcoholic fatty liver disease. You should use the general term NAFLD and reserve NASH only for those who have histologic evidence of steatohepatitis,” Dr. Reddy advised.

Overall, about 10% of patients with NAFLD have NASH. Limited data on the natural history of these conditions suggest that about 15%–20% of patients with steatosis will progress to steatohepatitis at some point. Of those, smaller numbers will go on to develop fibrosis, cirrhosis, and hepatocellular carcinoma. The exact percentages have varied widely in different studies.

Factors that predict progression from NAFLD to NASH include age greater than 45 years, type 2 diabetes, body mass index greater than 35 kg/m

Data pertaining to treatment of NAFLD are also limited, but weight management is considered a major priority for all patients because of proven benefits in cardiovascular risk profile.

Overall, about 10% of patients with nonalcoholic fatty liver disease have nonalcoholic steatohepatitis. DR. REDDY

PHILADELPHIA — Nonalcoholic fatty liver disease is emerging as a major health burden in the United States, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.

Often associated with obesity and underlying insulin resistance, nonalcoholic fatty liver disease (NAFLD) is believed to affect as much as 20%–30% of the U.S. population, said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.

There is some debate about the amount of alcohol ingestion permitted to make the distinction between alcoholic steatosis and NAFLD, which is defined as increased liver weight by 5%–10% as a result of fat accumulation (steatosis), in the absence of excessive alcohol consumption.

Most experts agree, however, that overall alcohol consumption of less than 20 g per day is well below that which would be associated with significant alcoholic liver disease, noted Dr. Reddy, who is also medical director of liver transplantation at the university.

Classification of NAFLD falls into four types: Type 1 (fatty liver alone) and type 2 (fat accumulation and lobular inflammation) are considered to be NAFLD alone. The more serious types 3 (fat accumulation and ballooning degeneration) and 4 (fat accumulation, ballooning degeneration, and either Mallory hyaline and/or fibrosis) are characterized as nonalcoholic steatohepatitis (NASH).

“There is a tendency to use the term NASH loosely in everyone who has nonalcoholic fatty liver disease. You should use the general term NAFLD and reserve NASH only for those who have histologic evidence of steatohepatitis,” Dr. Reddy advised.

Overall, about 10% of patients with NAFLD have NASH. Limited data on the natural history of these conditions suggest that about 15%–20% of patients with steatosis will progress to steatohepatitis at some point. Of those, smaller numbers will go on to develop fibrosis, cirrhosis, and hepatocellular carcinoma. The exact percentages have varied widely in different studies.

Factors that predict progression from NAFLD to NASH include age greater than 45 years, type 2 diabetes, body mass index greater than 35 kg/m

Data pertaining to treatment of NAFLD are also limited, but weight management is considered a major priority for all patients because of proven benefits in cardiovascular risk profile.

Overall, about 10% of patients with nonalcoholic fatty liver disease have nonalcoholic steatohepatitis. DR. REDDY

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

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

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

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

Panels of noninvasive markers of fibrosis and inflammation may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. Also, an ultrasonographic tool called FibroScan is being evaluated in Europe.

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

In hepatitis C patients with genotype 1, which has the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy. Biopsy can help determine the need for treatment in patients with side effects or in those who were previously treated and therefore less likely to respond to retreatment.

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

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

The presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, but there is no proven therapy for NAFLD. Absence of steatohepatitis or fibrosis might remove that motivation.

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

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

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

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

Panels of noninvasive markers of fibrosis and inflammation may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. Also, an ultrasonographic tool called FibroScan is being evaluated in Europe.

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

In hepatitis C patients with genotype 1, which has the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy. Biopsy can help determine the need for treatment in patients with side effects or in those who were previously treated and therefore less likely to respond to retreatment.

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

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

The presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, but there is no proven therapy for NAFLD. Absence of steatohepatitis or fibrosis might remove that motivation.

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

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

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

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

Panels of noninvasive markers of fibrosis and inflammation may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. Also, an ultrasonographic tool called FibroScan is being evaluated in Europe.

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

In hepatitis C patients with genotype 1, which has the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy. Biopsy can help determine the need for treatment in patients with side effects or in those who were previously treated and therefore less likely to respond to retreatment.

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

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

The presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, but there is no proven therapy for NAFLD. Absence of steatohepatitis or fibrosis might remove that motivation.

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons.

More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Data on race and ethnicity showed that TB rates in 2005 were 19.6 times higher among Asians, 8.3-fold greater among blacks, and 7.3 times greater among Hispanics, compared with whites. However, rates declined in almost all racial and ethnic populations from 2003 to 2005, with the greatest decrease among American Indians/Alaska Natives (14.4%) and Asians (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

As reported separately in the same issue of the MMWR, the first-ever data from the CDC and the World Health Organization on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during 2000–2004. Population-based data from the United States indicate a rate of 4%, compared with 19% in Latvia and 15% in South Korea (MMWR 2006;55:301–5).

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons.

More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Data on race and ethnicity showed that TB rates in 2005 were 19.6 times higher among Asians, 8.3-fold greater among blacks, and 7.3 times greater among Hispanics, compared with whites. However, rates declined in almost all racial and ethnic populations from 2003 to 2005, with the greatest decrease among American Indians/Alaska Natives (14.4%) and Asians (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

As reported separately in the same issue of the MMWR, the first-ever data from the CDC and the World Health Organization on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during 2000–2004. Population-based data from the United States indicate a rate of 4%, compared with 19% in Latvia and 15% in South Korea (MMWR 2006;55:301–5).

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons.

More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Data on race and ethnicity showed that TB rates in 2005 were 19.6 times higher among Asians, 8.3-fold greater among blacks, and 7.3 times greater among Hispanics, compared with whites. However, rates declined in almost all racial and ethnic populations from 2003 to 2005, with the greatest decrease among American Indians/Alaska Natives (14.4%) and Asians (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

As reported separately in the same issue of the MMWR, the first-ever data from the CDC and the World Health Organization on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during 2000–2004. Population-based data from the United States indicate a rate of 4%, compared with 19% in Latvia and 15% in South Korea (MMWR 2006;55:301–5).

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

In general, the MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The ESAR-VHP, on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so. Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both programs are still evolving, with current efforts underway to standardize the credentialing procedures and to increase pre-event training opportunities.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

In general, the MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The ESAR-VHP, on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so. Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both programs are still evolving, with current efforts underway to standardize the credentialing procedures and to increase pre-event training opportunities.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

In general, the MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The ESAR-VHP, on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so. Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both programs are still evolving, with current efforts underway to standardize the credentialing procedures and to increase pre-event training opportunities.

PHILADELPHIA — The American College of Physicians is calling for greater involvement of physicians in pandemic influenza preparedness than is specified in the U.S. government's plan.

The ACP's new policy paper, “The Health Care Response to Pandemic Influenza,” generally supports the U.S. Department of Health and Human Services' national strategic plan for responding to a possible pandemic influenza outbreak (www.pandemicflu.gov

The ACP document also faults the HHS plan for not providing enough detail about the logistics of rationing health care resources should the H5N1 influenza strain now circulating among birds in Asia and Europe emerge into a human pandemic.

A pandemic “will require all non-hospital-based health care providers … to be prepared to counsel, to diagnose, to treat, and to monitor patients outside of hospital settings in order to decrease the likelihood of surges that could and would overwhelm hospital capacity,” said Dr. Donna E. Sweet, then chair of the ACP Board of Regents, at a press briefing during the ACP's annual meeting.

The HHS plan is based on the assumption that an average of 20% of working adults would become ill during a community outbreak, and of those, 50%—about 45 million—would seek outpatient medical care over a 6- to 8-week period.

According to Dr. John A. Mitas II, ACP deputy executive vice president, “while the government's current plan begins to address the elements needed during [an influenza pandemic], it needs to go further to involve all physicians. It is critical that internists, who will be on the front lines of care should an outbreak occur, be involved. … ACP calls for a plan for hands-on clinical training of internists to address the public health crisis.”

ACP's position falls under five major headings:

▸ Physician involvement. Local task forces should be developed that include physicians from all practice settings. Federal or state agencies should coordinate the utilization, licensing, and registration of physician volunteers during public health emergencies.

▸ Surveillance, monitoring, and reporting. Health care providers should have access to two-way communication with public health authorities. Any necessary breaching of patient confidentiality should minimize harm while heeding applicable laws. Infection control measures must be clear and as minimally disruptive as possible. Physicians should not be penalized for failure to follow orders that are inappropriate or beyond their control.

▸ Vaccines and antivirals. It is essential to end chronic delays in vaccine delivery. ACP supports national procurement of enough vaccine to protect the entire U.S. population, and of antiviral medication for 25% of the U.S. population, with equitable distribution to states based on the number of high-risk individuals. Additional courses of antiviral drugs should be procured for all personnel in direct contact with patients.

▸ Ambulatory care. An effective response to pandemic influenza will require all non-hospital-based health care providers to counsel, diagnose, treat, and monitor patients outside of hospital settings in order to decrease the likelihood of surges that would overwhelm hospital capacity.

▸ Physician security. The safety of health care personnel must be provided for during public health emergencies. Those who store or administer vaccines, antiviral medications, and other supplies must be fully informed about preplanned security measures.

Asked about how realistic these goals are and in what time frame they might be achieved, Dr. Mitas responded: “The training could occur within a 6- to 12-month period, starting with the awareness. In terms of having the vaccine and the antiviral agents, that's going to take more time.”

“The education is easier than putting into place the physical system, the reporting system, the communication networks, the electronic technology,” Dr. Sweet said. “The hard part is we're not going to have enough [antivirals] or vaccine in the short period of time the way the progress is going right now.”

But “the planning has to be done now,” Dr. Sweet added. “It's going to be way too late when we see the first 10 cases.”

PHILADELPHIA — The American College of Physicians is calling for greater involvement of physicians in pandemic influenza preparedness than is specified in the U.S. government's plan.

The ACP's new policy paper, “The Health Care Response to Pandemic Influenza,” generally supports the U.S. Department of Health and Human Services' national strategic plan for responding to a possible pandemic influenza outbreak (www.pandemicflu.gov

The ACP document also faults the HHS plan for not providing enough detail about the logistics of rationing health care resources should the H5N1 influenza strain now circulating among birds in Asia and Europe emerge into a human pandemic.

A pandemic “will require all non-hospital-based health care providers … to be prepared to counsel, to diagnose, to treat, and to monitor patients outside of hospital settings in order to decrease the likelihood of surges that could and would overwhelm hospital capacity,” said Dr. Donna E. Sweet, then chair of the ACP Board of Regents, at a press briefing during the ACP's annual meeting.

The HHS plan is based on the assumption that an average of 20% of working adults would become ill during a community outbreak, and of those, 50%—about 45 million—would seek outpatient medical care over a 6- to 8-week period.

According to Dr. John A. Mitas II, ACP deputy executive vice president, “while the government's current plan begins to address the elements needed during [an influenza pandemic], it needs to go further to involve all physicians. It is critical that internists, who will be on the front lines of care should an outbreak occur, be involved. … ACP calls for a plan for hands-on clinical training of internists to address the public health crisis.”

ACP's position falls under five major headings:

▸ Physician involvement. Local task forces should be developed that include physicians from all practice settings. Federal or state agencies should coordinate the utilization, licensing, and registration of physician volunteers during public health emergencies.

▸ Surveillance, monitoring, and reporting. Health care providers should have access to two-way communication with public health authorities. Any necessary breaching of patient confidentiality should minimize harm while heeding applicable laws. Infection control measures must be clear and as minimally disruptive as possible. Physicians should not be penalized for failure to follow orders that are inappropriate or beyond their control.

▸ Vaccines and antivirals. It is essential to end chronic delays in vaccine delivery. ACP supports national procurement of enough vaccine to protect the entire U.S. population, and of antiviral medication for 25% of the U.S. population, with equitable distribution to states based on the number of high-risk individuals. Additional courses of antiviral drugs should be procured for all personnel in direct contact with patients.

▸ Ambulatory care. An effective response to pandemic influenza will require all non-hospital-based health care providers to counsel, diagnose, treat, and monitor patients outside of hospital settings in order to decrease the likelihood of surges that would overwhelm hospital capacity.

▸ Physician security. The safety of health care personnel must be provided for during public health emergencies. Those who store or administer vaccines, antiviral medications, and other supplies must be fully informed about preplanned security measures.

Asked about how realistic these goals are and in what time frame they might be achieved, Dr. Mitas responded: “The training could occur within a 6- to 12-month period, starting with the awareness. In terms of having the vaccine and the antiviral agents, that's going to take more time.”

“The education is easier than putting into place the physical system, the reporting system, the communication networks, the electronic technology,” Dr. Sweet said. “The hard part is we're not going to have enough [antivirals] or vaccine in the short period of time the way the progress is going right now.”

But “the planning has to be done now,” Dr. Sweet added. “It's going to be way too late when we see the first 10 cases.”

PHILADELPHIA — The American College of Physicians is calling for greater involvement of physicians in pandemic influenza preparedness than is specified in the U.S. government's plan.

The ACP's new policy paper, “The Health Care Response to Pandemic Influenza,” generally supports the U.S. Department of Health and Human Services' national strategic plan for responding to a possible pandemic influenza outbreak (www.pandemicflu.gov

The ACP document also faults the HHS plan for not providing enough detail about the logistics of rationing health care resources should the H5N1 influenza strain now circulating among birds in Asia and Europe emerge into a human pandemic.

A pandemic “will require all non-hospital-based health care providers … to be prepared to counsel, to diagnose, to treat, and to monitor patients outside of hospital settings in order to decrease the likelihood of surges that could and would overwhelm hospital capacity,” said Dr. Donna E. Sweet, then chair of the ACP Board of Regents, at a press briefing during the ACP's annual meeting.

The HHS plan is based on the assumption that an average of 20% of working adults would become ill during a community outbreak, and of those, 50%—about 45 million—would seek outpatient medical care over a 6- to 8-week period.

According to Dr. John A. Mitas II, ACP deputy executive vice president, “while the government's current plan begins to address the elements needed during [an influenza pandemic], it needs to go further to involve all physicians. It is critical that internists, who will be on the front lines of care should an outbreak occur, be involved. … ACP calls for a plan for hands-on clinical training of internists to address the public health crisis.”

ACP's position falls under five major headings:

▸ Physician involvement. Local task forces should be developed that include physicians from all practice settings. Federal or state agencies should coordinate the utilization, licensing, and registration of physician volunteers during public health emergencies.

▸ Surveillance, monitoring, and reporting. Health care providers should have access to two-way communication with public health authorities. Any necessary breaching of patient confidentiality should minimize harm while heeding applicable laws. Infection control measures must be clear and as minimally disruptive as possible. Physicians should not be penalized for failure to follow orders that are inappropriate or beyond their control.

▸ Vaccines and antivirals. It is essential to end chronic delays in vaccine delivery. ACP supports national procurement of enough vaccine to protect the entire U.S. population, and of antiviral medication for 25% of the U.S. population, with equitable distribution to states based on the number of high-risk individuals. Additional courses of antiviral drugs should be procured for all personnel in direct contact with patients.

▸ Ambulatory care. An effective response to pandemic influenza will require all non-hospital-based health care providers to counsel, diagnose, treat, and monitor patients outside of hospital settings in order to decrease the likelihood of surges that would overwhelm hospital capacity.

▸ Physician security. The safety of health care personnel must be provided for during public health emergencies. Those who store or administer vaccines, antiviral medications, and other supplies must be fully informed about preplanned security measures.

Asked about how realistic these goals are and in what time frame they might be achieved, Dr. Mitas responded: “The training could occur within a 6- to 12-month period, starting with the awareness. In terms of having the vaccine and the antiviral agents, that's going to take more time.”

“The education is easier than putting into place the physical system, the reporting system, the communication networks, the electronic technology,” Dr. Sweet said. “The hard part is we're not going to have enough [antivirals] or vaccine in the short period of time the way the progress is going right now.”

But “the planning has to be done now,” Dr. Sweet added. “It's going to be way too late when we see the first 10 cases.”

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.