Miriam E. Tucker

WASHINGTON — Hyperglycemia should be identified and vigorously treated in all hospitalized patients to improve medical and surgical outcomes, according to new guidelines from the American Association of Clinical Endocrinologists.

The guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients who have hyperglycemia upon admission, not just those with known diabetes.

Those previously recommended targets—iterated in a position statement from the American College of Endocrinology and the American Diabetes Association—include a blood glucose limit of no more than 110 mg/dL for patients in the intensive care unit; a fasting glucose level of 110 mg/dL for patients in noncritical care units; and a postprandial glucose limit of 180 mg/dL in noncritical care patients who can eat (Endocr. Pract. 2004;10:77–82).

“People with diabetes and high blood sugar [represent] an increasing percentage of hospitalized patients with serious problems which need special attention. …The findings and conclusions of this important conference will help to determine health care policies to improve patient care in all of our nation's hospitals,” Dr. Rhoda H. Cobin of Mount Sinai School of Medicine, New York, and ACE president, said at a press briefing following the meeting.

Among the findings and recommendations:

▸ Elevated blood sugars should be identified in all hospitalized patients.

▸ Hyperglycemia should be vigorously treated as soon as it is detected.

▸ Structured protocols for aggressive control of blood sugar in both intensive care units and other hospital settings should be implemented.

▸ Successful protocols for intensive glycemic control are available for use in intensive care units and other hospital settings. Several published protocols are available, and the guidelines allow institutions to choose those that best fit their resources and staff expertise: “The exact protocol is probably less important than its presence in an institution,” the guidelines state.

No longer acceptable, however, are the traditional “sliding scale” regimens. According to the document—and participants at the consensus conference—this “retroactive form of insulin replacement” is “inherently illogical,” has been associated with increased glycemic excursions, and is “potentially very dangerous” in certain settings, particularly among patients with type 1 diabetes.

The guidelines go on to state that when subcutaneous insulin is used, it should be done in the most physiologic way possible to achieve the best control. Use of oral hypoglycemic agents is discouraged for most hospitalized patients, although it may be acceptable in certain stable patients who are eating. Although hypoglycemia may be unavoidable as a result of aggressive treatment, it is usually mild, transient, and easily treated, and harm can be avoided, particularly when structured plans are in place.

Plans should be implemented for a smooth transition to outpatient care with appropriate diabetes management, particularly in patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state. Finally, the National Diabetes Quality Improvement Alliance should develop performance measures for the inpatient management of hyperglycemia and submit the measures to the National Quality Forum for the approval process which establishes these measures as standards for the nation.

The guidelines also encourage purchasers, payers, and accreditors to adopt standardized measures for use in their publicly reported measure sets, disease management accreditation programs, and pay-for-performance programs.

As a first step, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) is set to launch a voluntary inpatient diabetes care certification program in the first half of 2006, Charles A. Mowll, JCAHO's executive vice president for business development, government, and external relations announced at the conference.

WASHINGTON — Hyperglycemia should be identified and vigorously treated in all hospitalized patients to improve medical and surgical outcomes, according to new guidelines from the American Association of Clinical Endocrinologists.

The guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients who have hyperglycemia upon admission, not just those with known diabetes.

Those previously recommended targets—iterated in a position statement from the American College of Endocrinology and the American Diabetes Association—include a blood glucose limit of no more than 110 mg/dL for patients in the intensive care unit; a fasting glucose level of 110 mg/dL for patients in noncritical care units; and a postprandial glucose limit of 180 mg/dL in noncritical care patients who can eat (Endocr. Pract. 2004;10:77–82).

“People with diabetes and high blood sugar [represent] an increasing percentage of hospitalized patients with serious problems which need special attention. …The findings and conclusions of this important conference will help to determine health care policies to improve patient care in all of our nation's hospitals,” Dr. Rhoda H. Cobin of Mount Sinai School of Medicine, New York, and ACE president, said at a press briefing following the meeting.

Among the findings and recommendations:

▸ Elevated blood sugars should be identified in all hospitalized patients.

▸ Hyperglycemia should be vigorously treated as soon as it is detected.

▸ Structured protocols for aggressive control of blood sugar in both intensive care units and other hospital settings should be implemented.

▸ Successful protocols for intensive glycemic control are available for use in intensive care units and other hospital settings. Several published protocols are available, and the guidelines allow institutions to choose those that best fit their resources and staff expertise: “The exact protocol is probably less important than its presence in an institution,” the guidelines state.

No longer acceptable, however, are the traditional “sliding scale” regimens. According to the document—and participants at the consensus conference—this “retroactive form of insulin replacement” is “inherently illogical,” has been associated with increased glycemic excursions, and is “potentially very dangerous” in certain settings, particularly among patients with type 1 diabetes.

The guidelines go on to state that when subcutaneous insulin is used, it should be done in the most physiologic way possible to achieve the best control. Use of oral hypoglycemic agents is discouraged for most hospitalized patients, although it may be acceptable in certain stable patients who are eating. Although hypoglycemia may be unavoidable as a result of aggressive treatment, it is usually mild, transient, and easily treated, and harm can be avoided, particularly when structured plans are in place.

Plans should be implemented for a smooth transition to outpatient care with appropriate diabetes management, particularly in patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state. Finally, the National Diabetes Quality Improvement Alliance should develop performance measures for the inpatient management of hyperglycemia and submit the measures to the National Quality Forum for the approval process which establishes these measures as standards for the nation.

The guidelines also encourage purchasers, payers, and accreditors to adopt standardized measures for use in their publicly reported measure sets, disease management accreditation programs, and pay-for-performance programs.

As a first step, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) is set to launch a voluntary inpatient diabetes care certification program in the first half of 2006, Charles A. Mowll, JCAHO's executive vice president for business development, government, and external relations announced at the conference.

WASHINGTON — Hyperglycemia should be identified and vigorously treated in all hospitalized patients to improve medical and surgical outcomes, according to new guidelines from the American Association of Clinical Endocrinologists.

The guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients who have hyperglycemia upon admission, not just those with known diabetes.

Those previously recommended targets—iterated in a position statement from the American College of Endocrinology and the American Diabetes Association—include a blood glucose limit of no more than 110 mg/dL for patients in the intensive care unit; a fasting glucose level of 110 mg/dL for patients in noncritical care units; and a postprandial glucose limit of 180 mg/dL in noncritical care patients who can eat (Endocr. Pract. 2004;10:77–82).

“People with diabetes and high blood sugar [represent] an increasing percentage of hospitalized patients with serious problems which need special attention. …The findings and conclusions of this important conference will help to determine health care policies to improve patient care in all of our nation's hospitals,” Dr. Rhoda H. Cobin of Mount Sinai School of Medicine, New York, and ACE president, said at a press briefing following the meeting.

Among the findings and recommendations:

▸ Elevated blood sugars should be identified in all hospitalized patients.

▸ Hyperglycemia should be vigorously treated as soon as it is detected.

▸ Structured protocols for aggressive control of blood sugar in both intensive care units and other hospital settings should be implemented.

▸ Successful protocols for intensive glycemic control are available for use in intensive care units and other hospital settings. Several published protocols are available, and the guidelines allow institutions to choose those that best fit their resources and staff expertise: “The exact protocol is probably less important than its presence in an institution,” the guidelines state.

No longer acceptable, however, are the traditional “sliding scale” regimens. According to the document—and participants at the consensus conference—this “retroactive form of insulin replacement” is “inherently illogical,” has been associated with increased glycemic excursions, and is “potentially very dangerous” in certain settings, particularly among patients with type 1 diabetes.

The guidelines go on to state that when subcutaneous insulin is used, it should be done in the most physiologic way possible to achieve the best control. Use of oral hypoglycemic agents is discouraged for most hospitalized patients, although it may be acceptable in certain stable patients who are eating. Although hypoglycemia may be unavoidable as a result of aggressive treatment, it is usually mild, transient, and easily treated, and harm can be avoided, particularly when structured plans are in place.

Plans should be implemented for a smooth transition to outpatient care with appropriate diabetes management, particularly in patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state. Finally, the National Diabetes Quality Improvement Alliance should develop performance measures for the inpatient management of hyperglycemia and submit the measures to the National Quality Forum for the approval process which establishes these measures as standards for the nation.

The guidelines also encourage purchasers, payers, and accreditors to adopt standardized measures for use in their publicly reported measure sets, disease management accreditation programs, and pay-for-performance programs.

As a first step, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) is set to launch a voluntary inpatient diabetes care certification program in the first half of 2006, Charles A. Mowll, JCAHO's executive vice president for business development, government, and external relations announced at the conference.

Targeting blood glucose levels to below 110 mg/dL with insulin therapy prevented morbidity but did not significantly reduce mortality among patients in a medical intensive care unit, said Dr. Greet Van den Berghe and her associates, of Catholic University of Leuven, Belgium.

A total of 1,200 adult patients who were predicted to require medical intensive care for at least 3 days were randomized to either strict normalization of glucose levels (80–110 mg/dL) with the use of infused insulin, or to conventional therapy in which insulin was given only when the blood glucose level exceeded 215 mg/dL and stopped below 180 mg/dL (N. Engl. J. Med. 2006;354:449–61).

The intensive treatment group experienced significantly fewer newly acquired kidney injuries than did the conventionally treated patients (9% vs. 6%), were weaned earlier from mechanical ventilation (hazard ratio 1.21), and were discharged earlier from both the ICU (1.15) and from the hospital (1.16). There was no significant effect on bacteremia, the researchers reported.

Among the 1,200 patients in the intention-to-treat analysis, ICU and in-hospital mortality were not significantly reduced by intensive insulin therapy. At day 3, mortality was 2.8% of the 605 patients randomized to conventional treatment, compared with 3.9% of the 595 in the intensive treatment group. Total in-hospital deaths occurred in 40% and 37%, respectively.

However, when the 767 patients who stayed in the ICU for more than 3 days were examined separately, the in-hospital mortality was reduced significantly, from 53% of the 381 conventionally treated patients to 43% of the 386 in the intensive treatment group, Dr. Van den Berghe and her associates reported.

In contrast, among the 433 patients who stayed in the ICU less than 3 days, mortality was slightly—but not significantly—higher in the intensive treatment group. After censoring 65 patients for whom intensive care had been limited or withdrawn within 72 hours after ICU admission, the in-hospital mortality was 15% for the conventional treatment group and 17% with intensive treatment.

The most likely explanation for the difference in the effect of insulin therapy in the group as a whole compared with those staying in the ICU at least 3 days is that benefits from intensive insulin therapy take time to be realized. Because the intervention is aimed at preventing complications that occur during—and perhaps as a result of—intensive care, it wouldn't be expected to work if the patient has a high risk of death from the disease that prompted the ICU admission, they said.

The mortality findings from these medical ICU patients differ from what the authors reported previously in a study of 1,548 surgical ICU patients, for whom mortality at 12 months was 8% with conventional treatment versus 4.6% with intensive insulin therapy (N. Engl. J. Med. 2001;345:1359–67).

When complications resulting from intensive care contribute to an adverse outcome, a preventive strategy like intensive glucose control is likely to be effective. This would explain why patients with long stays in the medical ICU benefit more than those with short stays, as was shown in the surgical ICU, they said.

Hypoglycemia was more common among the intensively treated patients and was also identified as an independent risk factor for death. However, among those who had hypoglycemia, the intensively treated patients were less likely to die in the ICU than were the conventional treatment patients (46% vs. 67%).

Contributing writer Giancarlo La Giorgia assisted with this report.

Targeting blood glucose levels to below 110 mg/dL with insulin therapy prevented morbidity but did not significantly reduce mortality among patients in a medical intensive care unit, said Dr. Greet Van den Berghe and her associates, of Catholic University of Leuven, Belgium.

A total of 1,200 adult patients who were predicted to require medical intensive care for at least 3 days were randomized to either strict normalization of glucose levels (80–110 mg/dL) with the use of infused insulin, or to conventional therapy in which insulin was given only when the blood glucose level exceeded 215 mg/dL and stopped below 180 mg/dL (N. Engl. J. Med. 2006;354:449–61).

The intensive treatment group experienced significantly fewer newly acquired kidney injuries than did the conventionally treated patients (9% vs. 6%), were weaned earlier from mechanical ventilation (hazard ratio 1.21), and were discharged earlier from both the ICU (1.15) and from the hospital (1.16). There was no significant effect on bacteremia, the researchers reported.

Among the 1,200 patients in the intention-to-treat analysis, ICU and in-hospital mortality were not significantly reduced by intensive insulin therapy. At day 3, mortality was 2.8% of the 605 patients randomized to conventional treatment, compared with 3.9% of the 595 in the intensive treatment group. Total in-hospital deaths occurred in 40% and 37%, respectively.

However, when the 767 patients who stayed in the ICU for more than 3 days were examined separately, the in-hospital mortality was reduced significantly, from 53% of the 381 conventionally treated patients to 43% of the 386 in the intensive treatment group, Dr. Van den Berghe and her associates reported.

In contrast, among the 433 patients who stayed in the ICU less than 3 days, mortality was slightly—but not significantly—higher in the intensive treatment group. After censoring 65 patients for whom intensive care had been limited or withdrawn within 72 hours after ICU admission, the in-hospital mortality was 15% for the conventional treatment group and 17% with intensive treatment.

The most likely explanation for the difference in the effect of insulin therapy in the group as a whole compared with those staying in the ICU at least 3 days is that benefits from intensive insulin therapy take time to be realized. Because the intervention is aimed at preventing complications that occur during—and perhaps as a result of—intensive care, it wouldn't be expected to work if the patient has a high risk of death from the disease that prompted the ICU admission, they said.

The mortality findings from these medical ICU patients differ from what the authors reported previously in a study of 1,548 surgical ICU patients, for whom mortality at 12 months was 8% with conventional treatment versus 4.6% with intensive insulin therapy (N. Engl. J. Med. 2001;345:1359–67).

When complications resulting from intensive care contribute to an adverse outcome, a preventive strategy like intensive glucose control is likely to be effective. This would explain why patients with long stays in the medical ICU benefit more than those with short stays, as was shown in the surgical ICU, they said.

Hypoglycemia was more common among the intensively treated patients and was also identified as an independent risk factor for death. However, among those who had hypoglycemia, the intensively treated patients were less likely to die in the ICU than were the conventional treatment patients (46% vs. 67%).

Contributing writer Giancarlo La Giorgia assisted with this report.

Targeting blood glucose levels to below 110 mg/dL with insulin therapy prevented morbidity but did not significantly reduce mortality among patients in a medical intensive care unit, said Dr. Greet Van den Berghe and her associates, of Catholic University of Leuven, Belgium.

A total of 1,200 adult patients who were predicted to require medical intensive care for at least 3 days were randomized to either strict normalization of glucose levels (80–110 mg/dL) with the use of infused insulin, or to conventional therapy in which insulin was given only when the blood glucose level exceeded 215 mg/dL and stopped below 180 mg/dL (N. Engl. J. Med. 2006;354:449–61).

The intensive treatment group experienced significantly fewer newly acquired kidney injuries than did the conventionally treated patients (9% vs. 6%), were weaned earlier from mechanical ventilation (hazard ratio 1.21), and were discharged earlier from both the ICU (1.15) and from the hospital (1.16). There was no significant effect on bacteremia, the researchers reported.

Among the 1,200 patients in the intention-to-treat analysis, ICU and in-hospital mortality were not significantly reduced by intensive insulin therapy. At day 3, mortality was 2.8% of the 605 patients randomized to conventional treatment, compared with 3.9% of the 595 in the intensive treatment group. Total in-hospital deaths occurred in 40% and 37%, respectively.

However, when the 767 patients who stayed in the ICU for more than 3 days were examined separately, the in-hospital mortality was reduced significantly, from 53% of the 381 conventionally treated patients to 43% of the 386 in the intensive treatment group, Dr. Van den Berghe and her associates reported.

In contrast, among the 433 patients who stayed in the ICU less than 3 days, mortality was slightly—but not significantly—higher in the intensive treatment group. After censoring 65 patients for whom intensive care had been limited or withdrawn within 72 hours after ICU admission, the in-hospital mortality was 15% for the conventional treatment group and 17% with intensive treatment.

The most likely explanation for the difference in the effect of insulin therapy in the group as a whole compared with those staying in the ICU at least 3 days is that benefits from intensive insulin therapy take time to be realized. Because the intervention is aimed at preventing complications that occur during—and perhaps as a result of—intensive care, it wouldn't be expected to work if the patient has a high risk of death from the disease that prompted the ICU admission, they said.

The mortality findings from these medical ICU patients differ from what the authors reported previously in a study of 1,548 surgical ICU patients, for whom mortality at 12 months was 8% with conventional treatment versus 4.6% with intensive insulin therapy (N. Engl. J. Med. 2001;345:1359–67).

When complications resulting from intensive care contribute to an adverse outcome, a preventive strategy like intensive glucose control is likely to be effective. This would explain why patients with long stays in the medical ICU benefit more than those with short stays, as was shown in the surgical ICU, they said.

Hypoglycemia was more common among the intensively treated patients and was also identified as an independent risk factor for death. However, among those who had hypoglycemia, the intensively treated patients were less likely to die in the ICU than were the conventional treatment patients (46% vs. 67%).

Contributing writer Giancarlo La Giorgia assisted with this report.

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

Among 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 women accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

Of course, these data do not exclude the possibility that the higher prevalence of HSV-2 among women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen.

However, “as PID remains the most frequent gynecologic cause for emergency room visits as well as the most frequent infectious cause of infertility, confirmation and further exploration of these findings could have important clinical implications,” Dr. Cherpes and his associates wrote.

The conference was sponsored by the American Society for Microbiology.

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

Among 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 women accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

Of course, these data do not exclude the possibility that the higher prevalence of HSV-2 among women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen.

However, “as PID remains the most frequent gynecologic cause for emergency room visits as well as the most frequent infectious cause of infertility, confirmation and further exploration of these findings could have important clinical implications,” Dr. Cherpes and his associates wrote.

The conference was sponsored by the American Society for Microbiology.

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

Among 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 women accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

Of course, these data do not exclude the possibility that the higher prevalence of HSV-2 among women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen.

However, “as PID remains the most frequent gynecologic cause for emergency room visits as well as the most frequent infectious cause of infertility, confirmation and further exploration of these findings could have important clinical implications,” Dr. Cherpes and his associates wrote.

The conference was sponsored by the American Society for Microbiology.

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

In 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

These data do not exclude the possibility that the higher prevalence of HSV-2 in women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen, the investigators wrote.

The conference was sponsored by the American Society for Microbiology.

Source: Analytica International for Novartis Pharmaceuticals

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

In 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

These data do not exclude the possibility that the higher prevalence of HSV-2 in women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen, the investigators wrote.

The conference was sponsored by the American Society for Microbiology.

Source: Analytica International for Novartis Pharmaceuticals

WASHINGTON — Herpes simplex virus type 2 infection in women may be associated with an increased risk of pelvic inflammatory disease, Dr. Thomas L. Cherpes reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The role of chronic genital viral infections in the pathogenesis of pelvic inflammatory disease (PID) may be more significant than currently recognized, although no etiologic link has as yet been defined, noted Dr. Cherpes and his associates at the University of Pittsburgh.

A total of 725 nonpregnant women aged 15–30 years who were either diagnosed with a lower bacterial genital tract infection (purulent cervical discharge, untreated Neisseria gonorrhoeae or Chlamydia trachomatis infection, symptomatic bacterial vaginosis) or were at risk for such an infection (sexual contact with a male diagnosed with gonorrheal, chlamydial, or nongonococcal urethritis) were recruited from sexually transmitted disease clinics and gynecology clinics. Of those, 43% (309) were seropositive for herpes simplex virus type 2 (HSV-2).

Of the 86 women with acute endometritis, 55% (47) were HSV-2 seropositive, as were 51% (70) of the 136 women found to have plasma cell endometritis. Acute endometritis was independently associated with black race (odds ratio 1.7) as well as infections with C. trachomatis (3.3), N. gonorrhoeae (2.8), Trichomonas vaginalis (2.4), and HSV-2 (2.2). Black race also was associated with plasma cell endometritis (odds ratio 1.9), but HSV-2 was the only reproductive tract infection significantly associated with that condition (odds ratio 1.5), they reported.

Coinfection with HSV-2 and a genital tract bacterial pathogen significantly increased the likelihood of PID, compared with having one or the other alone. For example, the odds ratio for acute endometritis was 5.0 for women with chlamydia and 2.6 for those with HSV-2, compared with women who did not have those conditions. However, the odds ratio jumped to 7.3 for women coinfected with both. Similarly, women with gonorrhea alone had a 4.2-fold increased risk for acute endometritis, which rose to 6.0 if they were also infected with HSV-2.

In 471 of the women who underwent hysterosalpingography, 8.1% (38) had both HSV-2 infection and evidence of fallopian tube obstruction: Those 38 accounted for 19% of the 199 women who were HSV-2 positive and 54% of the 71 with fallopian tube blockage.

These data do not exclude the possibility that the higher prevalence of HSV-2 in women with PID may simply reflect a marker for sexual activity and/or the coacquisition of a PID-associated bacterial pathogen, the investigators wrote.

The conference was sponsored by the American Society for Microbiology.

Source: Analytica International for Novartis Pharmaceuticals

WASHINGTON — When it comes to human papillomavirus, U.S. clinicians who see the most patients with it are aware of the basics but aren't always up on the latest information, Dr. Nidhi Jain reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The finding comes from a survey of a nationally representative sampling from nine clinical specialties that care for substantial numbers of sexually active patients: The 4,305 respondents (to a total 6,906 mailed surveys) included family/general practice physicians (9%), general internists (7%), adolescent medicine specialists (10%), ob.gyns. (11%), dermatologists (12%), urologists (11%), nurse practitioners (15%), certified nurse midwives (15%), and physician assistants (12%).

A majority (89%) knew that “genital HPV [human papillomavirus] infection is fairly common in sexually active adults,” that infected individuals often lack signs or symptoms (95%), that an HPV infection increases the risk for cervical dysplasia and cancer (98%), and that treatment of external anogenital warts and cervical dysplasia/cancer does not always eliminate the infection (92% warts; 91% dysplasia/cancer).

But only 35% were aware of recent scientific evidence showing that most HPV infections clear without medical intervention, that anogenital warts do not increase the risk of cancer at the same site where the warts are located (38%), and that the HPV types associated with warts are not the same as the types associated with cervical dysplasia (47%).

Of all the specialists, ob. gyns. had the best overall knowledge of HPV. In the group as a whole, clinicians who use HPV testing gave more correct responses than did those who don't use the tests, Dr. Jain said at the conference, sponsored by the American Society for Microbiology.

“However, even the highest percentages were sometimes very low,” said Dr. Jain, a medical officer at the Centers for Disease Control and Prevention, Atlanta.

WASHINGTON — When it comes to human papillomavirus, U.S. clinicians who see the most patients with it are aware of the basics but aren't always up on the latest information, Dr. Nidhi Jain reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The finding comes from a survey of a nationally representative sampling from nine clinical specialties that care for substantial numbers of sexually active patients: The 4,305 respondents (to a total 6,906 mailed surveys) included family/general practice physicians (9%), general internists (7%), adolescent medicine specialists (10%), ob.gyns. (11%), dermatologists (12%), urologists (11%), nurse practitioners (15%), certified nurse midwives (15%), and physician assistants (12%).

A majority (89%) knew that “genital HPV [human papillomavirus] infection is fairly common in sexually active adults,” that infected individuals often lack signs or symptoms (95%), that an HPV infection increases the risk for cervical dysplasia and cancer (98%), and that treatment of external anogenital warts and cervical dysplasia/cancer does not always eliminate the infection (92% warts; 91% dysplasia/cancer).

But only 35% were aware of recent scientific evidence showing that most HPV infections clear without medical intervention, that anogenital warts do not increase the risk of cancer at the same site where the warts are located (38%), and that the HPV types associated with warts are not the same as the types associated with cervical dysplasia (47%).

Of all the specialists, ob. gyns. had the best overall knowledge of HPV. In the group as a whole, clinicians who use HPV testing gave more correct responses than did those who don't use the tests, Dr. Jain said at the conference, sponsored by the American Society for Microbiology.

“However, even the highest percentages were sometimes very low,” said Dr. Jain, a medical officer at the Centers for Disease Control and Prevention, Atlanta.

WASHINGTON — When it comes to human papillomavirus, U.S. clinicians who see the most patients with it are aware of the basics but aren't always up on the latest information, Dr. Nidhi Jain reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The finding comes from a survey of a nationally representative sampling from nine clinical specialties that care for substantial numbers of sexually active patients: The 4,305 respondents (to a total 6,906 mailed surveys) included family/general practice physicians (9%), general internists (7%), adolescent medicine specialists (10%), ob.gyns. (11%), dermatologists (12%), urologists (11%), nurse practitioners (15%), certified nurse midwives (15%), and physician assistants (12%).

A majority (89%) knew that “genital HPV [human papillomavirus] infection is fairly common in sexually active adults,” that infected individuals often lack signs or symptoms (95%), that an HPV infection increases the risk for cervical dysplasia and cancer (98%), and that treatment of external anogenital warts and cervical dysplasia/cancer does not always eliminate the infection (92% warts; 91% dysplasia/cancer).

But only 35% were aware of recent scientific evidence showing that most HPV infections clear without medical intervention, that anogenital warts do not increase the risk of cancer at the same site where the warts are located (38%), and that the HPV types associated with warts are not the same as the types associated with cervical dysplasia (47%).

Of all the specialists, ob. gyns. had the best overall knowledge of HPV. In the group as a whole, clinicians who use HPV testing gave more correct responses than did those who don't use the tests, Dr. Jain said at the conference, sponsored by the American Society for Microbiology.

“However, even the highest percentages were sometimes very low,” said Dr. Jain, a medical officer at the Centers for Disease Control and Prevention, Atlanta.

FT. LAUDERDALE, FLA. — Zoledronic acid, if approved for the treatment of Paget's disease of bone, could prove a slightly cheaper therapeutic option than other available therapies in the setting of a managed care formulary, Lee S. Stern said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

That conclusion is based on a budget impact analysis sponsored by Novartis Pharmaceuticals Corp., the maker of zoledronic acid (Zometa). Ms. Stern, a health economist with Analytica International, New York, said a typical 1-million-member managed care organization that adds the drug to its formulary could expect to save about $2,000 per year.

At press time, Zometa is licensed solely for the treatment of hypercalcemia of malignancy. The Food and Drug Administration is reviewing an indication for the drug's use in Paget's disease and could act as early as this month. Zoledronic acid is administered as an intravenous infusion.

Based on the speed and extent of disease suppression with zoledronic acid, and the drug's ability to suppress bone turnover for up to 2 years, it is viewed as an advance over available IV and oral bisphosphonates. In a pivotal randomized, double-blind, controlled trial, 96% of patients with Paget's disease had a therapeutic response to zoledronic acid, compared with a response in 74% receiving 60 days of oral risedronate. Response was achieved in a median of 64 days with zoledronic acid and 89 days with oral risedronate (N. Engl. J. Med. 2005;353:898–908).

“Given the clinical profile of zoledronic acid in terms of these higher response rates, we can expect a lower overall cost to the managed care plan,” said Ms. Stern.

The analysis modeled the introduction of zoledronic acid into the formulary of a theoretical managed care organization with 1 million members and an annual growth rate of 0.85% per year. Using data from the literature, market research, and other sources, the model assumed that the prevalence of Paget's disease is 1.04% and that 3.24 individuals per 100,000 would be newly diagnosed each year.

Further, the prevalence of Paget's disease is falling by about 5% per year, and the annual mortality among diagnosed individuals is about 1.8%, Ms. Stern said.

In 2004, an estimated 7.6% of a managed care plan's Paget's disease population would have been treated with bisphosphonates. In 2005, zoledronic acid would take away 2% of that market. If given the Paget's indication, that percentage would increase to 11% in 2006, to 18% in 2007, and to 22% in 2008 and thereafter.

Annual treatment costs were derived from a model that weighed the efficacy (response and relapse rates) for each of the bisphosphonates based on clinical trial results, the type and extent of medical and pharmacy resource use based on expert opinion, and cost estimates from official fee schedules and published sources.

Compared with the other oral and intravenous bisphosphonates, zoledronic acid had the lowest mean annual treatment cost per patient, $829. Alendronate was second, at $923, followed by risedronate ($938), pamidronate ($1,277), etidronate ($1,712), and tiludronate ($2,039). In the case of zoledronic acid, “The high response rate and ease of use offset the actual cost of the drug,” Ms. Stern said.

Overall, the projected overall annual cost savings to the managed care organization would be $2,078, a per patient per year savings of $2.70, and a per patient per month savings of $0.22. While this might look small, “Any kind of savings to managed care is always good news and usually means that the drug will have good pull-through once it gets approved,” she noted.

FT. LAUDERDALE, FLA. — Zoledronic acid, if approved for the treatment of Paget's disease of bone, could prove a slightly cheaper therapeutic option than other available therapies in the setting of a managed care formulary, Lee S. Stern said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

That conclusion is based on a budget impact analysis sponsored by Novartis Pharmaceuticals Corp., the maker of zoledronic acid (Zometa). Ms. Stern, a health economist with Analytica International, New York, said a typical 1-million-member managed care organization that adds the drug to its formulary could expect to save about $2,000 per year.

At press time, Zometa is licensed solely for the treatment of hypercalcemia of malignancy. The Food and Drug Administration is reviewing an indication for the drug's use in Paget's disease and could act as early as this month. Zoledronic acid is administered as an intravenous infusion.

Based on the speed and extent of disease suppression with zoledronic acid, and the drug's ability to suppress bone turnover for up to 2 years, it is viewed as an advance over available IV and oral bisphosphonates. In a pivotal randomized, double-blind, controlled trial, 96% of patients with Paget's disease had a therapeutic response to zoledronic acid, compared with a response in 74% receiving 60 days of oral risedronate. Response was achieved in a median of 64 days with zoledronic acid and 89 days with oral risedronate (N. Engl. J. Med. 2005;353:898–908).

“Given the clinical profile of zoledronic acid in terms of these higher response rates, we can expect a lower overall cost to the managed care plan,” said Ms. Stern.

The analysis modeled the introduction of zoledronic acid into the formulary of a theoretical managed care organization with 1 million members and an annual growth rate of 0.85% per year. Using data from the literature, market research, and other sources, the model assumed that the prevalence of Paget's disease is 1.04% and that 3.24 individuals per 100,000 would be newly diagnosed each year.

Further, the prevalence of Paget's disease is falling by about 5% per year, and the annual mortality among diagnosed individuals is about 1.8%, Ms. Stern said.

In 2004, an estimated 7.6% of a managed care plan's Paget's disease population would have been treated with bisphosphonates. In 2005, zoledronic acid would take away 2% of that market. If given the Paget's indication, that percentage would increase to 11% in 2006, to 18% in 2007, and to 22% in 2008 and thereafter.

Annual treatment costs were derived from a model that weighed the efficacy (response and relapse rates) for each of the bisphosphonates based on clinical trial results, the type and extent of medical and pharmacy resource use based on expert opinion, and cost estimates from official fee schedules and published sources.

Compared with the other oral and intravenous bisphosphonates, zoledronic acid had the lowest mean annual treatment cost per patient, $829. Alendronate was second, at $923, followed by risedronate ($938), pamidronate ($1,277), etidronate ($1,712), and tiludronate ($2,039). In the case of zoledronic acid, “The high response rate and ease of use offset the actual cost of the drug,” Ms. Stern said.

Overall, the projected overall annual cost savings to the managed care organization would be $2,078, a per patient per year savings of $2.70, and a per patient per month savings of $0.22. While this might look small, “Any kind of savings to managed care is always good news and usually means that the drug will have good pull-through once it gets approved,” she noted.

FT. LAUDERDALE, FLA. — Zoledronic acid, if approved for the treatment of Paget's disease of bone, could prove a slightly cheaper therapeutic option than other available therapies in the setting of a managed care formulary, Lee S. Stern said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

That conclusion is based on a budget impact analysis sponsored by Novartis Pharmaceuticals Corp., the maker of zoledronic acid (Zometa). Ms. Stern, a health economist with Analytica International, New York, said a typical 1-million-member managed care organization that adds the drug to its formulary could expect to save about $2,000 per year.

At press time, Zometa is licensed solely for the treatment of hypercalcemia of malignancy. The Food and Drug Administration is reviewing an indication for the drug's use in Paget's disease and could act as early as this month. Zoledronic acid is administered as an intravenous infusion.

Based on the speed and extent of disease suppression with zoledronic acid, and the drug's ability to suppress bone turnover for up to 2 years, it is viewed as an advance over available IV and oral bisphosphonates. In a pivotal randomized, double-blind, controlled trial, 96% of patients with Paget's disease had a therapeutic response to zoledronic acid, compared with a response in 74% receiving 60 days of oral risedronate. Response was achieved in a median of 64 days with zoledronic acid and 89 days with oral risedronate (N. Engl. J. Med. 2005;353:898–908).

“Given the clinical profile of zoledronic acid in terms of these higher response rates, we can expect a lower overall cost to the managed care plan,” said Ms. Stern.

The analysis modeled the introduction of zoledronic acid into the formulary of a theoretical managed care organization with 1 million members and an annual growth rate of 0.85% per year. Using data from the literature, market research, and other sources, the model assumed that the prevalence of Paget's disease is 1.04% and that 3.24 individuals per 100,000 would be newly diagnosed each year.

Further, the prevalence of Paget's disease is falling by about 5% per year, and the annual mortality among diagnosed individuals is about 1.8%, Ms. Stern said.

In 2004, an estimated 7.6% of a managed care plan's Paget's disease population would have been treated with bisphosphonates. In 2005, zoledronic acid would take away 2% of that market. If given the Paget's indication, that percentage would increase to 11% in 2006, to 18% in 2007, and to 22% in 2008 and thereafter.

Annual treatment costs were derived from a model that weighed the efficacy (response and relapse rates) for each of the bisphosphonates based on clinical trial results, the type and extent of medical and pharmacy resource use based on expert opinion, and cost estimates from official fee schedules and published sources.

Compared with the other oral and intravenous bisphosphonates, zoledronic acid had the lowest mean annual treatment cost per patient, $829. Alendronate was second, at $923, followed by risedronate ($938), pamidronate ($1,277), etidronate ($1,712), and tiludronate ($2,039). In the case of zoledronic acid, “The high response rate and ease of use offset the actual cost of the drug,” Ms. Stern said.

Overall, the projected overall annual cost savings to the managed care organization would be $2,078, a per patient per year savings of $2.70, and a per patient per month savings of $0.22. While this might look small, “Any kind of savings to managed care is always good news and usually means that the drug will have good pull-through once it gets approved,” she noted.

FT. LAUDERDALE, FLA. — Screening for vitamin D deficiency should be part of the initial evaluation of patients with Paget's disease, Dr. Jennifer J. Kelly and Dr. Arnold M. Moses said in a poster presentation at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Blood collected from 37 patients (mean age 72) at their initial visit to a metabolic bone clinic revealed that just three (8%) had levels of 25(OH)D considered to be optimal (greater than 32 ng/mL), while 21 (58%) were vitamin D deficient (below 20 ng/mL), said the investigators, of the State University of New York Upstate Medical University, Syracuse.

The median 25(OH)D level among the 24 men in the group was 20 ng/mL, compared with just 13 ng/mL among the 13 women. Women were more likely than men (5 vs. 2) to be grossly deficient (0–9 ng/mL), while men were in the majority in the intermediate range between 10 and 32 ng/mL (20 men vs. 7 women). Levels greater than 32 ng/mL were seen in only two men and one woman.

Season also influenced 25(OH)D levels, which were on average 9 ng/mL higher during the “light” months (May-September) than during the “dark” period of November-March. Of the 13 patients whose blood had been collected during the light months, 7 (54%) had 25(OH)D levels of 20 ng/mL or above, compared with just 3 (20%) of the 15 sampled during the dark months. Women had lower median vitamin D levels than men in both the light and dark months.

FT. LAUDERDALE, FLA. — Screening for vitamin D deficiency should be part of the initial evaluation of patients with Paget's disease, Dr. Jennifer J. Kelly and Dr. Arnold M. Moses said in a poster presentation at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Blood collected from 37 patients (mean age 72) at their initial visit to a metabolic bone clinic revealed that just three (8%) had levels of 25(OH)D considered to be optimal (greater than 32 ng/mL), while 21 (58%) were vitamin D deficient (below 20 ng/mL), said the investigators, of the State University of New York Upstate Medical University, Syracuse.

The median 25(OH)D level among the 24 men in the group was 20 ng/mL, compared with just 13 ng/mL among the 13 women. Women were more likely than men (5 vs. 2) to be grossly deficient (0–9 ng/mL), while men were in the majority in the intermediate range between 10 and 32 ng/mL (20 men vs. 7 women). Levels greater than 32 ng/mL were seen in only two men and one woman.

Season also influenced 25(OH)D levels, which were on average 9 ng/mL higher during the “light” months (May-September) than during the “dark” period of November-March. Of the 13 patients whose blood had been collected during the light months, 7 (54%) had 25(OH)D levels of 20 ng/mL or above, compared with just 3 (20%) of the 15 sampled during the dark months. Women had lower median vitamin D levels than men in both the light and dark months.

FT. LAUDERDALE, FLA. — Screening for vitamin D deficiency should be part of the initial evaluation of patients with Paget's disease, Dr. Jennifer J. Kelly and Dr. Arnold M. Moses said in a poster presentation at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Blood collected from 37 patients (mean age 72) at their initial visit to a metabolic bone clinic revealed that just three (8%) had levels of 25(OH)D considered to be optimal (greater than 32 ng/mL), while 21 (58%) were vitamin D deficient (below 20 ng/mL), said the investigators, of the State University of New York Upstate Medical University, Syracuse.

The median 25(OH)D level among the 24 men in the group was 20 ng/mL, compared with just 13 ng/mL among the 13 women. Women were more likely than men (5 vs. 2) to be grossly deficient (0–9 ng/mL), while men were in the majority in the intermediate range between 10 and 32 ng/mL (20 men vs. 7 women). Levels greater than 32 ng/mL were seen in only two men and one woman.

Season also influenced 25(OH)D levels, which were on average 9 ng/mL higher during the “light” months (May-September) than during the “dark” period of November-March. Of the 13 patients whose blood had been collected during the light months, 7 (54%) had 25(OH)D levels of 20 ng/mL or above, compared with just 3 (20%) of the 15 sampled during the dark months. Women had lower median vitamin D levels than men in both the light and dark months.

FT. LAUDERDALE, FLA. — Biochemical screening of patients with Paget's disease of bone should always include measurement of parathyroid hormone levels, Dr. Maria Luisa Brandi advised at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

The coexistence of Paget's disease and hyperparathyroidism, first described in 1948, is still not well understood. In studies, approximately 12%–18% of Paget's disease patients have elevated levels of parathyroid hormone (PTH), most of which represent secondary hyperparathyroidism. Yet measurement of PTH is still not routine, and “hyperparathyroidism in Paget's disease of bone is often overlooked,” said Dr. Brandi, professor of endocrinology and metabolism at the University of Florence, Italy.

Both Paget's disease and hyperparathyroidism are capable of causing bone pain, and bone biomarkers are elevated in both disorders. Increased marrow fibrosis and vascularity are common histologic features of both. But the two disorders differ in several histologic features, she said at the conference, also sponsored by the National Institutes of Health and Columbia University, New York.

Increasing lines of evidence suggest that the cooccurrence of primary hyperparathyroidism with Paget's disease is due to the chance association of two diseases that are common in the elderly. Autopsy studies in Paget's disease patients failed to uncover consistent parathyroid gland abnormalities. Furthermore, the prevalence and gender distribution of primary hyperparathyroidism in Paget's disease resembles that of the elderly population as a whole.

Most genetic studies have failed to find overlapping genes in the two disorders, but recent data suggest there might be some interactions among gene products, she noted.

Regardless of etiology, an excess of PTH is likely to have an exaggerated impact at skeletal sites affected by Paget's disease. Therefore, biochemical screening of patients with Paget's disease should include evaluation of serum calcium, phosphate, and PTH. Parathyroidectomy is indicated in patients found to have both disorders. Conversely, patients who have primary hyperparathyroidism and high bone turnover after parathyroidectomy should undergo diagnostic screening for Paget's disease, Dr. Brandi recommended.

FT. LAUDERDALE, FLA. — Biochemical screening of patients with Paget's disease of bone should always include measurement of parathyroid hormone levels, Dr. Maria Luisa Brandi advised at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

The coexistence of Paget's disease and hyperparathyroidism, first described in 1948, is still not well understood. In studies, approximately 12%–18% of Paget's disease patients have elevated levels of parathyroid hormone (PTH), most of which represent secondary hyperparathyroidism. Yet measurement of PTH is still not routine, and “hyperparathyroidism in Paget's disease of bone is often overlooked,” said Dr. Brandi, professor of endocrinology and metabolism at the University of Florence, Italy.

Both Paget's disease and hyperparathyroidism are capable of causing bone pain, and bone biomarkers are elevated in both disorders. Increased marrow fibrosis and vascularity are common histologic features of both. But the two disorders differ in several histologic features, she said at the conference, also sponsored by the National Institutes of Health and Columbia University, New York.

Increasing lines of evidence suggest that the cooccurrence of primary hyperparathyroidism with Paget's disease is due to the chance association of two diseases that are common in the elderly. Autopsy studies in Paget's disease patients failed to uncover consistent parathyroid gland abnormalities. Furthermore, the prevalence and gender distribution of primary hyperparathyroidism in Paget's disease resembles that of the elderly population as a whole.

Most genetic studies have failed to find overlapping genes in the two disorders, but recent data suggest there might be some interactions among gene products, she noted.

Regardless of etiology, an excess of PTH is likely to have an exaggerated impact at skeletal sites affected by Paget's disease. Therefore, biochemical screening of patients with Paget's disease should include evaluation of serum calcium, phosphate, and PTH. Parathyroidectomy is indicated in patients found to have both disorders. Conversely, patients who have primary hyperparathyroidism and high bone turnover after parathyroidectomy should undergo diagnostic screening for Paget's disease, Dr. Brandi recommended.

FT. LAUDERDALE, FLA. — Biochemical screening of patients with Paget's disease of bone should always include measurement of parathyroid hormone levels, Dr. Maria Luisa Brandi advised at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

The coexistence of Paget's disease and hyperparathyroidism, first described in 1948, is still not well understood. In studies, approximately 12%–18% of Paget's disease patients have elevated levels of parathyroid hormone (PTH), most of which represent secondary hyperparathyroidism. Yet measurement of PTH is still not routine, and “hyperparathyroidism in Paget's disease of bone is often overlooked,” said Dr. Brandi, professor of endocrinology and metabolism at the University of Florence, Italy.

Both Paget's disease and hyperparathyroidism are capable of causing bone pain, and bone biomarkers are elevated in both disorders. Increased marrow fibrosis and vascularity are common histologic features of both. But the two disorders differ in several histologic features, she said at the conference, also sponsored by the National Institutes of Health and Columbia University, New York.

Increasing lines of evidence suggest that the cooccurrence of primary hyperparathyroidism with Paget's disease is due to the chance association of two diseases that are common in the elderly. Autopsy studies in Paget's disease patients failed to uncover consistent parathyroid gland abnormalities. Furthermore, the prevalence and gender distribution of primary hyperparathyroidism in Paget's disease resembles that of the elderly population as a whole.

Most genetic studies have failed to find overlapping genes in the two disorders, but recent data suggest there might be some interactions among gene products, she noted.

Regardless of etiology, an excess of PTH is likely to have an exaggerated impact at skeletal sites affected by Paget's disease. Therefore, biochemical screening of patients with Paget's disease should include evaluation of serum calcium, phosphate, and PTH. Parathyroidectomy is indicated in patients found to have both disorders. Conversely, patients who have primary hyperparathyroidism and high bone turnover after parathyroidectomy should undergo diagnostic screening for Paget's disease, Dr. Brandi recommended.

BETHESDA, MD. — A fully “closed-loop” insulin pump delivery system is still several steps away, but steady progress is being made toward the creation of a functional artificial pancreas that provides far better glucose control for type 1 diabetic patients than is currently available.

That was the consensus from a meeting sponsored by the National Institutes of Health and the Juvenile Diabetes Research Foundation in which scientists, clinicians, and industry representatives came together to address the current state of the art and to discuss ways of overcoming technical obstacles.

Over the last 2 decades, external insulin pump therapy has become a standard treatment option for patients with type 1 diabetes. Current pumps are “open loop,” meaning that they require input from the user, both in setting the background (basal) infusion rate and for delivering premeal boluses based on the blood glucose level and anticipated carbohydrate consumption. Recent advances have incorporated a continuous glucose monitor into the system along with algorithms that estimate the bolus dose, but the technology still requires user input—and therefore is subject to some degree of error.

The main problem isn't in delivering the insulin. Rather, it's overcoming the numerous technical barriers to developing a real-time sensor that can respond to the current glucose level, as well as its rate and direction of change. Moreover, algorithms linking the sensor with the delivery system must also account for all the other physiologic factors that contribute to glucose homeostasis, such as incretins, free fatty acids, and counterregulatory hormones.

“There are three elements to a closed-loop system: the delivery device, the sensing device, and linking algorithms. Each element is very complex, and difficult to develop. Each must really be developed independently before you can put together a complete closed-loop system,” explained Dr. Christopher D. Saudek, professor of medicine at the Johns Hopkins University and director of the Johns Hopkins Diabetes Center, Baltimore.

But Dr. Saudek, who has been researching open-loop implantable pumps for the last 25 years, still sees mechanical insulin delivery as more immediately promising than a biological approach such as islet or stem cell transplantation. “Either would be a cure if it worked reliably and well. But the biological approach still requires enormous basic science breakthroughs before it will help people. The mechanical approach is applied research. It's a matter of refining techniques we have that work.”

The preference for mechanical “cure” certainly applies to children and adolescents, for whom the need for lifelong immune suppression following transplantation is undesirable, said Dr. William V. Tamborlane, professor of pediatrics and chief of pediatric endocrinology at Yale University, New Haven, Conn.

Maintaining good diabetes control is particularly difficult in adolescents, and not just because they tend to be rebellious and noncompliant. Teenagers experience wide swings in glucose because their unique physiology makes them more insulin resistant while paradoxically more vulnerable to hypoglycemia, especially at night. “The development of a closed-loop artificial pancreas is the most likely candidate to revolutionize the treatment of childhood type 1 diabetes in the foreseeable future,” Dr. Tamborlane said.

He reviewed preliminary results of short-term (30–35 hours), closed-loop control in seven adolescents with type 1 diabetes, using Medtronic Minimed's external glucose sensor and infusion pump (information about both available at www.minimed.com

However, despite multiple premeal infusion adjustments, peak postmeal blood glucose levels often exceeded 200 mg/dL, particularly after breakfast.

Currently under investigation is “semi-automatic” or “hybrid” strategy, where the patient manually administers a partial, priming dose of insulin prior to eating, with the remaining insulin regulated by the system. Although not closed loop, this would be a great improvement over currently available technology, Dr. Tamborlane noted.

The same would be true of an imperfect completely closed loop: “Now, when my patients forget to bolus, their blood glucose goes up to 400 [mg/dL]. At least with a closed loop, it would only go to 250. … Maybe we don't need to aim for perfect,” he said.

Similar postmeal problems were seen among 22 young adults with type 1 diabetes in whom a system developed by Roche Diagnostics (www.roche-diagnostics.com

This system utilized an empirical glucose-control algorithm based on a calculation of the current glucose concentration and its gradient, the remaining effect of already-infused insulin, the amount of carbohydrate intake, and patient-specific factors such as basal insulin requirement and insulin-to-carbohydrate ratio. As with the adolescents, overnight values approached the target of 120 mg/dL, with only half the variability that occurred among the patients without the controller. But blood glucose values remained highly variable throughout meal times, again particularly after breakfast.

“Our data suggest that a semi-closed loop system using the subcutaneous route for glucose measurement and insulin application is possible. Although the time delay of insulin action means that a 'feed-forward' insulin dose is necessary, during nighttime the feedback part of the algorithm is able to achieve good control,” Dr. Freckmann said.

Indeed, such time delays will always occur with sensors that monitor glucose in the interstitial fluid, according to Dr. Jeffrey I. Joseph, director of the Artificial Pancreas Center at Thomas Jefferson University, Philadelphia.

Minimed Medtronic has been developing a glucose sensor that measures changes in the oxygen concentration within the superior vena cava, where it is implanted for the long term. Using the vascular sensor and a peritoneal implantable insulin delivery device, French researchers have demonstrated the feasibility of a closed-loop system.

Although the physiological delay with this system is tiny, here the problem is longevity. From a practical standpoint, any implantable device would need to work for at least 7 years to be viable. Currently the Minimed system must be replaced every 12–16 months, Dr. Joseph noted.

Since 1996, he has been working with another major insulin pump manufacturer, Animas (www.animascorp.com

At least two other companies are forging ahead with continuous glucose sensors. Abbott's Navigator, currently under review by the Food and Drug Administration, would be used to make therapeutic decisions, although calibration by the user would still be required (www.abbottdiabetescare.comwww.dexcom.com

BETHESDA, MD. — A fully “closed-loop” insulin pump delivery system is still several steps away, but steady progress is being made toward the creation of a functional artificial pancreas that provides far better glucose control for type 1 diabetic patients than is currently available.

That was the consensus from a meeting sponsored by the National Institutes of Health and the Juvenile Diabetes Research Foundation in which scientists, clinicians, and industry representatives came together to address the current state of the art and to discuss ways of overcoming technical obstacles.

Over the last 2 decades, external insulin pump therapy has become a standard treatment option for patients with type 1 diabetes. Current pumps are “open loop,” meaning that they require input from the user, both in setting the background (basal) infusion rate and for delivering premeal boluses based on the blood glucose level and anticipated carbohydrate consumption. Recent advances have incorporated a continuous glucose monitor into the system along with algorithms that estimate the bolus dose, but the technology still requires user input—and therefore is subject to some degree of error.

The main problem isn't in delivering the insulin. Rather, it's overcoming the numerous technical barriers to developing a real-time sensor that can respond to the current glucose level, as well as its rate and direction of change. Moreover, algorithms linking the sensor with the delivery system must also account for all the other physiologic factors that contribute to glucose homeostasis, such as incretins, free fatty acids, and counterregulatory hormones.

“There are three elements to a closed-loop system: the delivery device, the sensing device, and linking algorithms. Each element is very complex, and difficult to develop. Each must really be developed independently before you can put together a complete closed-loop system,” explained Dr. Christopher D. Saudek, professor of medicine at the Johns Hopkins University and director of the Johns Hopkins Diabetes Center, Baltimore.

But Dr. Saudek, who has been researching open-loop implantable pumps for the last 25 years, still sees mechanical insulin delivery as more immediately promising than a biological approach such as islet or stem cell transplantation. “Either would be a cure if it worked reliably and well. But the biological approach still requires enormous basic science breakthroughs before it will help people. The mechanical approach is applied research. It's a matter of refining techniques we have that work.”

The preference for mechanical “cure” certainly applies to children and adolescents, for whom the need for lifelong immune suppression following transplantation is undesirable, said Dr. William V. Tamborlane, professor of pediatrics and chief of pediatric endocrinology at Yale University, New Haven, Conn.

Maintaining good diabetes control is particularly difficult in adolescents, and not just because they tend to be rebellious and noncompliant. Teenagers experience wide swings in glucose because their unique physiology makes them more insulin resistant while paradoxically more vulnerable to hypoglycemia, especially at night. “The development of a closed-loop artificial pancreas is the most likely candidate to revolutionize the treatment of childhood type 1 diabetes in the foreseeable future,” Dr. Tamborlane said.

He reviewed preliminary results of short-term (30–35 hours), closed-loop control in seven adolescents with type 1 diabetes, using Medtronic Minimed's external glucose sensor and infusion pump (information about both available at www.minimed.com

However, despite multiple premeal infusion adjustments, peak postmeal blood glucose levels often exceeded 200 mg/dL, particularly after breakfast.

Currently under investigation is “semi-automatic” or “hybrid” strategy, where the patient manually administers a partial, priming dose of insulin prior to eating, with the remaining insulin regulated by the system. Although not closed loop, this would be a great improvement over currently available technology, Dr. Tamborlane noted.

The same would be true of an imperfect completely closed loop: “Now, when my patients forget to bolus, their blood glucose goes up to 400 [mg/dL]. At least with a closed loop, it would only go to 250. … Maybe we don't need to aim for perfect,” he said.

Similar postmeal problems were seen among 22 young adults with type 1 diabetes in whom a system developed by Roche Diagnostics (www.roche-diagnostics.com

This system utilized an empirical glucose-control algorithm based on a calculation of the current glucose concentration and its gradient, the remaining effect of already-infused insulin, the amount of carbohydrate intake, and patient-specific factors such as basal insulin requirement and insulin-to-carbohydrate ratio. As with the adolescents, overnight values approached the target of 120 mg/dL, with only half the variability that occurred among the patients without the controller. But blood glucose values remained highly variable throughout meal times, again particularly after breakfast.

“Our data suggest that a semi-closed loop system using the subcutaneous route for glucose measurement and insulin application is possible. Although the time delay of insulin action means that a 'feed-forward' insulin dose is necessary, during nighttime the feedback part of the algorithm is able to achieve good control,” Dr. Freckmann said.

Indeed, such time delays will always occur with sensors that monitor glucose in the interstitial fluid, according to Dr. Jeffrey I. Joseph, director of the Artificial Pancreas Center at Thomas Jefferson University, Philadelphia.

Minimed Medtronic has been developing a glucose sensor that measures changes in the oxygen concentration within the superior vena cava, where it is implanted for the long term. Using the vascular sensor and a peritoneal implantable insulin delivery device, French researchers have demonstrated the feasibility of a closed-loop system.

Although the physiological delay with this system is tiny, here the problem is longevity. From a practical standpoint, any implantable device would need to work for at least 7 years to be viable. Currently the Minimed system must be replaced every 12–16 months, Dr. Joseph noted.

Since 1996, he has been working with another major insulin pump manufacturer, Animas (www.animascorp.com

At least two other companies are forging ahead with continuous glucose sensors. Abbott's Navigator, currently under review by the Food and Drug Administration, would be used to make therapeutic decisions, although calibration by the user would still be required (www.abbottdiabetescare.comwww.dexcom.com

BETHESDA, MD. — A fully “closed-loop” insulin pump delivery system is still several steps away, but steady progress is being made toward the creation of a functional artificial pancreas that provides far better glucose control for type 1 diabetic patients than is currently available.

That was the consensus from a meeting sponsored by the National Institutes of Health and the Juvenile Diabetes Research Foundation in which scientists, clinicians, and industry representatives came together to address the current state of the art and to discuss ways of overcoming technical obstacles.

Over the last 2 decades, external insulin pump therapy has become a standard treatment option for patients with type 1 diabetes. Current pumps are “open loop,” meaning that they require input from the user, both in setting the background (basal) infusion rate and for delivering premeal boluses based on the blood glucose level and anticipated carbohydrate consumption. Recent advances have incorporated a continuous glucose monitor into the system along with algorithms that estimate the bolus dose, but the technology still requires user input—and therefore is subject to some degree of error.

The main problem isn't in delivering the insulin. Rather, it's overcoming the numerous technical barriers to developing a real-time sensor that can respond to the current glucose level, as well as its rate and direction of change. Moreover, algorithms linking the sensor with the delivery system must also account for all the other physiologic factors that contribute to glucose homeostasis, such as incretins, free fatty acids, and counterregulatory hormones.

“There are three elements to a closed-loop system: the delivery device, the sensing device, and linking algorithms. Each element is very complex, and difficult to develop. Each must really be developed independently before you can put together a complete closed-loop system,” explained Dr. Christopher D. Saudek, professor of medicine at the Johns Hopkins University and director of the Johns Hopkins Diabetes Center, Baltimore.

But Dr. Saudek, who has been researching open-loop implantable pumps for the last 25 years, still sees mechanical insulin delivery as more immediately promising than a biological approach such as islet or stem cell transplantation. “Either would be a cure if it worked reliably and well. But the biological approach still requires enormous basic science breakthroughs before it will help people. The mechanical approach is applied research. It's a matter of refining techniques we have that work.”

The preference for mechanical “cure” certainly applies to children and adolescents, for whom the need for lifelong immune suppression following transplantation is undesirable, said Dr. William V. Tamborlane, professor of pediatrics and chief of pediatric endocrinology at Yale University, New Haven, Conn.

Maintaining good diabetes control is particularly difficult in adolescents, and not just because they tend to be rebellious and noncompliant. Teenagers experience wide swings in glucose because their unique physiology makes them more insulin resistant while paradoxically more vulnerable to hypoglycemia, especially at night. “The development of a closed-loop artificial pancreas is the most likely candidate to revolutionize the treatment of childhood type 1 diabetes in the foreseeable future,” Dr. Tamborlane said.

He reviewed preliminary results of short-term (30–35 hours), closed-loop control in seven adolescents with type 1 diabetes, using Medtronic Minimed's external glucose sensor and infusion pump (information about both available at www.minimed.com

However, despite multiple premeal infusion adjustments, peak postmeal blood glucose levels often exceeded 200 mg/dL, particularly after breakfast.

Currently under investigation is “semi-automatic” or “hybrid” strategy, where the patient manually administers a partial, priming dose of insulin prior to eating, with the remaining insulin regulated by the system. Although not closed loop, this would be a great improvement over currently available technology, Dr. Tamborlane noted.

The same would be true of an imperfect completely closed loop: “Now, when my patients forget to bolus, their blood glucose goes up to 400 [mg/dL]. At least with a closed loop, it would only go to 250. … Maybe we don't need to aim for perfect,” he said.

Similar postmeal problems were seen among 22 young adults with type 1 diabetes in whom a system developed by Roche Diagnostics (www.roche-diagnostics.com

This system utilized an empirical glucose-control algorithm based on a calculation of the current glucose concentration and its gradient, the remaining effect of already-infused insulin, the amount of carbohydrate intake, and patient-specific factors such as basal insulin requirement and insulin-to-carbohydrate ratio. As with the adolescents, overnight values approached the target of 120 mg/dL, with only half the variability that occurred among the patients without the controller. But blood glucose values remained highly variable throughout meal times, again particularly after breakfast.

“Our data suggest that a semi-closed loop system using the subcutaneous route for glucose measurement and insulin application is possible. Although the time delay of insulin action means that a 'feed-forward' insulin dose is necessary, during nighttime the feedback part of the algorithm is able to achieve good control,” Dr. Freckmann said.

Indeed, such time delays will always occur with sensors that monitor glucose in the interstitial fluid, according to Dr. Jeffrey I. Joseph, director of the Artificial Pancreas Center at Thomas Jefferson University, Philadelphia.

Minimed Medtronic has been developing a glucose sensor that measures changes in the oxygen concentration within the superior vena cava, where it is implanted for the long term. Using the vascular sensor and a peritoneal implantable insulin delivery device, French researchers have demonstrated the feasibility of a closed-loop system.

Although the physiological delay with this system is tiny, here the problem is longevity. From a practical standpoint, any implantable device would need to work for at least 7 years to be viable. Currently the Minimed system must be replaced every 12–16 months, Dr. Joseph noted.

Since 1996, he has been working with another major insulin pump manufacturer, Animas (www.animascorp.com

At least two other companies are forging ahead with continuous glucose sensors. Abbott's Navigator, currently under review by the Food and Drug Administration, would be used to make therapeutic decisions, although calibration by the user would still be required (www.abbottdiabetescare.comwww.dexcom.com

WASHINGTON — Quebec's massive outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices were likely to blame.

That conclusion, from an analysis of four Canadian hospitals headed by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces (68 prescriptions per 100 inhabitants per year, compared with the national average of 79/100).

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

Comparing affected with unaffected hospitals, there was no significant relation between number of CDAD cases per 1,000 admissions and daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any antibiotic class, Dr. Weiss and his associates said at the meeting sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved markedly in 2004–2005 following substantial investment by the provincial government and implementation of stringent infection control measures such as environmental cleaning with bleach, contact precautions, early detection of cases, and hand-washing with soap and water.

WASHINGTON — Quebec's massive outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices were likely to blame.

That conclusion, from an analysis of four Canadian hospitals headed by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces (68 prescriptions per 100 inhabitants per year, compared with the national average of 79/100).

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

Comparing affected with unaffected hospitals, there was no significant relation between number of CDAD cases per 1,000 admissions and daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any antibiotic class, Dr. Weiss and his associates said at the meeting sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved markedly in 2004–2005 following substantial investment by the provincial government and implementation of stringent infection control measures such as environmental cleaning with bleach, contact precautions, early detection of cases, and hand-washing with soap and water.

WASHINGTON — Quebec's massive outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices were likely to blame.

That conclusion, from an analysis of four Canadian hospitals headed by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces (68 prescriptions per 100 inhabitants per year, compared with the national average of 79/100).

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

Comparing affected with unaffected hospitals, there was no significant relation between number of CDAD cases per 1,000 admissions and daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any antibiotic class, Dr. Weiss and his associates said at the meeting sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved markedly in 2004–2005 following substantial investment by the provincial government and implementation of stringent infection control measures such as environmental cleaning with bleach, contact precautions, early detection of cases, and hand-washing with soap and water.