Miriam E. Tucker

Children receiving an investigational conjugate pneumococcal vaccine that uses a carrier protein derived from Haemophilus influenzae experience a one-third reduction in acute otitis media episodes compared with controls, said Dr. Roman Prymula and associates of the University of Defense, Hradec Králové, Czech Republic.

The vaccine, GlaxoSmithKline Inc.'s Streptorix, combines the seven strains of Streptococcus pneumoniae that are currently included in Wyeth's Prevnar (4, 6B, 9V, 14, 18C, 19F, and 23F) with four additional strains (1, 3, 5, and 7F). And in contrast to Prevnar, in which the seven strains are conjugated to a nontoxic mutant of diphtheria toxin (CRM 197), the 11 pneumococcal serotypes of this investigational vaccine—hereafter called the protein D conjugate vaccine—are conjugated to a carrier protein derived from H. influenzae, thereby providing protection against disease caused by that organism as well, the investigators said (Lancet 2006;367:740–8).

A total of 4,968 infants were randomized to receive doses of the protein D conjugate vaccine, or hepatitis A vaccine as a control, at 3, 4, 5, and 12–15 months of age.

During follow-up through 24–27 months of age, clinical episodes of acute otitis media (AOM) occurred in 366 protein D conjugate vaccine recipients and 553 controls, of which 333 and 499, respectively, were recorded in the per-protocol analysis. The overall incidence of AOM was 83.3 cases per 1,000 person-years with the protein D conjugate vaccine, compared with 125.2 per 1,000 person-years for the controls.

Efficacy of the protein D conjugate vaccine against the first episode of AOM caused by vaccine pneumococcal serotypes was 52.6% in both the per-protocol and intention-to-treat groups; efficacy against the first episode of AOM caused by nontypable H. influenzae was above 30% for both cohorts, but only significant for the intent-to-treat analysis (32.7%). Overall protective efficacy against clinical AOM episodes was 33.6%, reported Dr. Prymula, a consultant to GlaxoSmithKline, and associates. Safety data after the primary series—available for 2,489 infants in the protein D conjugate vaccine group and 2,479 controls who received hepatitis A vaccine—showed no significant differences in the number of unsolicited adverse events reported within 31 days after vaccination (48% vs. 50%), or in the number of events judged to be casually related to the vaccine (2.5% vs. 3.0%).

Total adverse event rates after the booster and rates of serious adverse events also did not differ significantly between the two groups in this study, which was supported by GlaxoSmithKline Biologicals, Rixensart, Belgium.

Children receiving an investigational conjugate pneumococcal vaccine that uses a carrier protein derived from Haemophilus influenzae experience a one-third reduction in acute otitis media episodes compared with controls, said Dr. Roman Prymula and associates of the University of Defense, Hradec Králové, Czech Republic.

The vaccine, GlaxoSmithKline Inc.'s Streptorix, combines the seven strains of Streptococcus pneumoniae that are currently included in Wyeth's Prevnar (4, 6B, 9V, 14, 18C, 19F, and 23F) with four additional strains (1, 3, 5, and 7F). And in contrast to Prevnar, in which the seven strains are conjugated to a nontoxic mutant of diphtheria toxin (CRM 197), the 11 pneumococcal serotypes of this investigational vaccine—hereafter called the protein D conjugate vaccine—are conjugated to a carrier protein derived from H. influenzae, thereby providing protection against disease caused by that organism as well, the investigators said (Lancet 2006;367:740–8).

A total of 4,968 infants were randomized to receive doses of the protein D conjugate vaccine, or hepatitis A vaccine as a control, at 3, 4, 5, and 12–15 months of age.

During follow-up through 24–27 months of age, clinical episodes of acute otitis media (AOM) occurred in 366 protein D conjugate vaccine recipients and 553 controls, of which 333 and 499, respectively, were recorded in the per-protocol analysis. The overall incidence of AOM was 83.3 cases per 1,000 person-years with the protein D conjugate vaccine, compared with 125.2 per 1,000 person-years for the controls.

Efficacy of the protein D conjugate vaccine against the first episode of AOM caused by vaccine pneumococcal serotypes was 52.6% in both the per-protocol and intention-to-treat groups; efficacy against the first episode of AOM caused by nontypable H. influenzae was above 30% for both cohorts, but only significant for the intent-to-treat analysis (32.7%). Overall protective efficacy against clinical AOM episodes was 33.6%, reported Dr. Prymula, a consultant to GlaxoSmithKline, and associates. Safety data after the primary series—available for 2,489 infants in the protein D conjugate vaccine group and 2,479 controls who received hepatitis A vaccine—showed no significant differences in the number of unsolicited adverse events reported within 31 days after vaccination (48% vs. 50%), or in the number of events judged to be casually related to the vaccine (2.5% vs. 3.0%).

Total adverse event rates after the booster and rates of serious adverse events also did not differ significantly between the two groups in this study, which was supported by GlaxoSmithKline Biologicals, Rixensart, Belgium.

Children receiving an investigational conjugate pneumococcal vaccine that uses a carrier protein derived from Haemophilus influenzae experience a one-third reduction in acute otitis media episodes compared with controls, said Dr. Roman Prymula and associates of the University of Defense, Hradec Králové, Czech Republic.

The vaccine, GlaxoSmithKline Inc.'s Streptorix, combines the seven strains of Streptococcus pneumoniae that are currently included in Wyeth's Prevnar (4, 6B, 9V, 14, 18C, 19F, and 23F) with four additional strains (1, 3, 5, and 7F). And in contrast to Prevnar, in which the seven strains are conjugated to a nontoxic mutant of diphtheria toxin (CRM 197), the 11 pneumococcal serotypes of this investigational vaccine—hereafter called the protein D conjugate vaccine—are conjugated to a carrier protein derived from H. influenzae, thereby providing protection against disease caused by that organism as well, the investigators said (Lancet 2006;367:740–8).

A total of 4,968 infants were randomized to receive doses of the protein D conjugate vaccine, or hepatitis A vaccine as a control, at 3, 4, 5, and 12–15 months of age.

During follow-up through 24–27 months of age, clinical episodes of acute otitis media (AOM) occurred in 366 protein D conjugate vaccine recipients and 553 controls, of which 333 and 499, respectively, were recorded in the per-protocol analysis. The overall incidence of AOM was 83.3 cases per 1,000 person-years with the protein D conjugate vaccine, compared with 125.2 per 1,000 person-years for the controls.

Efficacy of the protein D conjugate vaccine against the first episode of AOM caused by vaccine pneumococcal serotypes was 52.6% in both the per-protocol and intention-to-treat groups; efficacy against the first episode of AOM caused by nontypable H. influenzae was above 30% for both cohorts, but only significant for the intent-to-treat analysis (32.7%). Overall protective efficacy against clinical AOM episodes was 33.6%, reported Dr. Prymula, a consultant to GlaxoSmithKline, and associates. Safety data after the primary series—available for 2,489 infants in the protein D conjugate vaccine group and 2,479 controls who received hepatitis A vaccine—showed no significant differences in the number of unsolicited adverse events reported within 31 days after vaccination (48% vs. 50%), or in the number of events judged to be casually related to the vaccine (2.5% vs. 3.0%).

Total adverse event rates after the booster and rates of serious adverse events also did not differ significantly between the two groups in this study, which was supported by GlaxoSmithKline Biologicals, Rixensart, Belgium.

ATLANTA — Most internists and family physicians would recommend the herpes zoster vaccine to their older patients despite concerns about the vaccine's cost and reimbursement for its administration, Dr. Allison Kempe reported at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The findings came from a national survey of internists and family physicians conducted by Dr. Kempe and her associates at the University of Colorado, Denver, in November and December 2005.

The U.S. Food and Drug Administration is currently reviewing the licensure application for Zostavax, which was filed by Merck & Co. in April 2005. In June 2005, the vaccine received widespread media coverage with the publication of a study showing 51% efficacy in preventing herpes zoster, 66.5% efficacy against postherpetic neuralgia, and 61% reduction in pain in adults aged 60 and older (N. Engl. J. Med. 2005;352:2271–84).

Less than 10% of the surveyed physicians expressed concern about the fact that the vaccine must be kept frozen rather than refrigerated, yet previous experience with other live virus vaccines in primary care settings suggests this might be a bigger problem than many physicians realize, Dr. Gregory S. Wallace of the CDC told the advisory committee in a separate presentation.

Of the 270 general internists and 325 family physicians who participated in the survey (response rates of 62% and 76%, respectively), 35% “strongly” agreed that herpes zoster and postherpetic neuralgia cause significant burden among older patients, while another 46% “somewhat” agreed.

The percentage of physicians who strongly agreed that the burden of the two disorders was “sufficient enough to warrant a vaccine” was significantly higher with regard to patients aged 60–79 years, compared with patients aged 50–59 years (40% vs. 15% among internists and 29% vs. 17% among family physicians).

Overall, physicians of both specialties reported being somewhat or very likely to recommend the vaccine for all patients over 50 years, but were significantly more likely to recommend it to patients aged 60 and older than to those aged 50–59 (79% vs. 57% among internists and 78% vs. 60% among family physicians).

Despite their overall support for the vaccine, respondents did perceive several potential barriers to administering it. “Lack of reimbursement” topped the list, with 76% saying that would “definitely” be a barrier or would be “somewhat” of a barrier. “Patients unwilling to pay if not covered by insurance” and “up-front costs to purchase vaccine” were the second and third most important barriers, respectively.

In addition to the issue of freezer storage, other potential barriers cited by less than 10% of respondents included “concerns about safely administering a live attenuated virus to patients with chronic medical conditions,” and the “fact that vaccine will not be licensed for immunosuppressed patients.”

The low level of concern for those two issues appears justified: There were no major safety problems in the published study, in which 90% of the 38,546 subjects had at least one prior medical condition, including more than 20% each with arthritis and hypertension, Dr. Paula Annunziato of Merck told the committee.

Immunosuppressed individuals were excluded from the study, and none of the survey respondents had treated or referred any such patients for herpes zoster or postherpetic neuralgia in the previous year, Dr. Kempe said.

But freezer storage, which is required for all live virus vaccines, may indeed turn out to be a problem in many practices, according to the CDC's Dr. Wallace.

In one previous study of more than 700 primary care providers, 18% of freezers were being kept too warm for proper storage of varicella vaccine, measles-mumps-rubella-varicella vaccine, or live attenuated influenza vaccine (Flumist), all of which must be kept at or below 5° F (Am. J. Prev. Med. 2002;23:246–53). Another study of 221 private provider offices found that 17% of freezers were too warm (Pediatrics 2001;107:e100–4).

Recently, it has become apparent that the opposite is a problem, too: In order to keep the freezer cold enough for live virus vaccines, the refrigerator compartment may become too cold, which is damaging to inactivated vaccines that are stored there (MMWR 2003;52:1023–5). This is a particular problem in small dormitory-style refrigerators without a separate freezer section; these are unacceptable for storing vaccines, Dr. Wallace said.

ATLANTA — Most internists and family physicians would recommend the herpes zoster vaccine to their older patients despite concerns about the vaccine's cost and reimbursement for its administration, Dr. Allison Kempe reported at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The findings came from a national survey of internists and family physicians conducted by Dr. Kempe and her associates at the University of Colorado, Denver, in November and December 2005.

The U.S. Food and Drug Administration is currently reviewing the licensure application for Zostavax, which was filed by Merck & Co. in April 2005. In June 2005, the vaccine received widespread media coverage with the publication of a study showing 51% efficacy in preventing herpes zoster, 66.5% efficacy against postherpetic neuralgia, and 61% reduction in pain in adults aged 60 and older (N. Engl. J. Med. 2005;352:2271–84).

Less than 10% of the surveyed physicians expressed concern about the fact that the vaccine must be kept frozen rather than refrigerated, yet previous experience with other live virus vaccines in primary care settings suggests this might be a bigger problem than many physicians realize, Dr. Gregory S. Wallace of the CDC told the advisory committee in a separate presentation.

Of the 270 general internists and 325 family physicians who participated in the survey (response rates of 62% and 76%, respectively), 35% “strongly” agreed that herpes zoster and postherpetic neuralgia cause significant burden among older patients, while another 46% “somewhat” agreed.

The percentage of physicians who strongly agreed that the burden of the two disorders was “sufficient enough to warrant a vaccine” was significantly higher with regard to patients aged 60–79 years, compared with patients aged 50–59 years (40% vs. 15% among internists and 29% vs. 17% among family physicians).

Overall, physicians of both specialties reported being somewhat or very likely to recommend the vaccine for all patients over 50 years, but were significantly more likely to recommend it to patients aged 60 and older than to those aged 50–59 (79% vs. 57% among internists and 78% vs. 60% among family physicians).

Despite their overall support for the vaccine, respondents did perceive several potential barriers to administering it. “Lack of reimbursement” topped the list, with 76% saying that would “definitely” be a barrier or would be “somewhat” of a barrier. “Patients unwilling to pay if not covered by insurance” and “up-front costs to purchase vaccine” were the second and third most important barriers, respectively.

In addition to the issue of freezer storage, other potential barriers cited by less than 10% of respondents included “concerns about safely administering a live attenuated virus to patients with chronic medical conditions,” and the “fact that vaccine will not be licensed for immunosuppressed patients.”

The low level of concern for those two issues appears justified: There were no major safety problems in the published study, in which 90% of the 38,546 subjects had at least one prior medical condition, including more than 20% each with arthritis and hypertension, Dr. Paula Annunziato of Merck told the committee.

Immunosuppressed individuals were excluded from the study, and none of the survey respondents had treated or referred any such patients for herpes zoster or postherpetic neuralgia in the previous year, Dr. Kempe said.

But freezer storage, which is required for all live virus vaccines, may indeed turn out to be a problem in many practices, according to the CDC's Dr. Wallace.

In one previous study of more than 700 primary care providers, 18% of freezers were being kept too warm for proper storage of varicella vaccine, measles-mumps-rubella-varicella vaccine, or live attenuated influenza vaccine (Flumist), all of which must be kept at or below 5° F (Am. J. Prev. Med. 2002;23:246–53). Another study of 221 private provider offices found that 17% of freezers were too warm (Pediatrics 2001;107:e100–4).

Recently, it has become apparent that the opposite is a problem, too: In order to keep the freezer cold enough for live virus vaccines, the refrigerator compartment may become too cold, which is damaging to inactivated vaccines that are stored there (MMWR 2003;52:1023–5). This is a particular problem in small dormitory-style refrigerators without a separate freezer section; these are unacceptable for storing vaccines, Dr. Wallace said.

ATLANTA — Most internists and family physicians would recommend the herpes zoster vaccine to their older patients despite concerns about the vaccine's cost and reimbursement for its administration, Dr. Allison Kempe reported at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The findings came from a national survey of internists and family physicians conducted by Dr. Kempe and her associates at the University of Colorado, Denver, in November and December 2005.

The U.S. Food and Drug Administration is currently reviewing the licensure application for Zostavax, which was filed by Merck & Co. in April 2005. In June 2005, the vaccine received widespread media coverage with the publication of a study showing 51% efficacy in preventing herpes zoster, 66.5% efficacy against postherpetic neuralgia, and 61% reduction in pain in adults aged 60 and older (N. Engl. J. Med. 2005;352:2271–84).

Less than 10% of the surveyed physicians expressed concern about the fact that the vaccine must be kept frozen rather than refrigerated, yet previous experience with other live virus vaccines in primary care settings suggests this might be a bigger problem than many physicians realize, Dr. Gregory S. Wallace of the CDC told the advisory committee in a separate presentation.

Of the 270 general internists and 325 family physicians who participated in the survey (response rates of 62% and 76%, respectively), 35% “strongly” agreed that herpes zoster and postherpetic neuralgia cause significant burden among older patients, while another 46% “somewhat” agreed.

The percentage of physicians who strongly agreed that the burden of the two disorders was “sufficient enough to warrant a vaccine” was significantly higher with regard to patients aged 60–79 years, compared with patients aged 50–59 years (40% vs. 15% among internists and 29% vs. 17% among family physicians).

Overall, physicians of both specialties reported being somewhat or very likely to recommend the vaccine for all patients over 50 years, but were significantly more likely to recommend it to patients aged 60 and older than to those aged 50–59 (79% vs. 57% among internists and 78% vs. 60% among family physicians).

Despite their overall support for the vaccine, respondents did perceive several potential barriers to administering it. “Lack of reimbursement” topped the list, with 76% saying that would “definitely” be a barrier or would be “somewhat” of a barrier. “Patients unwilling to pay if not covered by insurance” and “up-front costs to purchase vaccine” were the second and third most important barriers, respectively.

In addition to the issue of freezer storage, other potential barriers cited by less than 10% of respondents included “concerns about safely administering a live attenuated virus to patients with chronic medical conditions,” and the “fact that vaccine will not be licensed for immunosuppressed patients.”

The low level of concern for those two issues appears justified: There were no major safety problems in the published study, in which 90% of the 38,546 subjects had at least one prior medical condition, including more than 20% each with arthritis and hypertension, Dr. Paula Annunziato of Merck told the committee.

Immunosuppressed individuals were excluded from the study, and none of the survey respondents had treated or referred any such patients for herpes zoster or postherpetic neuralgia in the previous year, Dr. Kempe said.

But freezer storage, which is required for all live virus vaccines, may indeed turn out to be a problem in many practices, according to the CDC's Dr. Wallace.

In one previous study of more than 700 primary care providers, 18% of freezers were being kept too warm for proper storage of varicella vaccine, measles-mumps-rubella-varicella vaccine, or live attenuated influenza vaccine (Flumist), all of which must be kept at or below 5° F (Am. J. Prev. Med. 2002;23:246–53). Another study of 221 private provider offices found that 17% of freezers were too warm (Pediatrics 2001;107:e100–4).

Recently, it has become apparent that the opposite is a problem, too: In order to keep the freezer cold enough for live virus vaccines, the refrigerator compartment may become too cold, which is damaging to inactivated vaccines that are stored there (MMWR 2003;52:1023–5). This is a particular problem in small dormitory-style refrigerators without a separate freezer section; these are unacceptable for storing vaccines, Dr. Wallace said.

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 new guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients found to 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 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 among patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state.

Finally, the National Diabetes Quality Improvement Alliance (www.nationaldiabetesalliance.org

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 new guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients found to 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 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 among patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state.

Finally, the National Diabetes Quality Improvement Alliance (www.nationaldiabetesalliance.org

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 new guidelines, presented at the conclusion of a 2-day consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association, provide specific strategies for achieving previously recommended targets in all patients found to 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 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 among patients who are newly diagnosed with diabetes during their hospital stay, the guidelines state.

Finally, the National Diabetes Quality Improvement Alliance (www.nationaldiabetesalliance.org

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the Portland Diabetic Project, a prospective, nonrandomized interventional study of the relationship between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards (www.portlandprotocol.org

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been gradually ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, Dr. Furnary reported. Indeed, mortality among CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality among nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% among diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value. Rates of other types of infection, postoperative transfusion, and new-onset atrial fibrillation were also found to be independently affected by 3-BG. Length of stay is also significantly related to 3-BG, by approximately 1 day for every 77-mg/dL increase.

In all, the Portland data thus far point to the need for change in current hospital practice. “It begs us to do something different, to not just report if a patient is diabetic or not,” Dr. Furnary commented.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, agreed. He summarized data from other recent studies of non-ICU populations that come to the same conclusion, including one of 1,253 patients with acute MI in whom in-hospital mortality did not differ between diabetic and nondiabetic patients, but was significantly greater among those with hyperglycemia on admission (defined as plasma glucose greater than 198 mg/dL) in both diabetic (10% vs. 5%) and nondiabetic (24% vs. 6%) patients (Am. Heart J. 2005;150:814–20).

According to Dr. Hirsch, two major trials published in 2005 that also support the same conclusion have been misinterpreted as negative. One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis showed that fasting blood glucose at baseline and during the study strongly predicted mortality (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the Portland Diabetic Project, a prospective, nonrandomized interventional study of the relationship between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards (www.portlandprotocol.org

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been gradually ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, Dr. Furnary reported. Indeed, mortality among CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality among nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% among diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value. Rates of other types of infection, postoperative transfusion, and new-onset atrial fibrillation were also found to be independently affected by 3-BG. Length of stay is also significantly related to 3-BG, by approximately 1 day for every 77-mg/dL increase.

In all, the Portland data thus far point to the need for change in current hospital practice. “It begs us to do something different, to not just report if a patient is diabetic or not,” Dr. Furnary commented.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, agreed. He summarized data from other recent studies of non-ICU populations that come to the same conclusion, including one of 1,253 patients with acute MI in whom in-hospital mortality did not differ between diabetic and nondiabetic patients, but was significantly greater among those with hyperglycemia on admission (defined as plasma glucose greater than 198 mg/dL) in both diabetic (10% vs. 5%) and nondiabetic (24% vs. 6%) patients (Am. Heart J. 2005;150:814–20).

According to Dr. Hirsch, two major trials published in 2005 that also support the same conclusion have been misinterpreted as negative. One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis showed that fasting blood glucose at baseline and during the study strongly predicted mortality (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the Portland Diabetic Project, a prospective, nonrandomized interventional study of the relationship between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards (www.portlandprotocol.org

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been gradually ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, Dr. Furnary reported. Indeed, mortality among CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality among nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% among diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value. Rates of other types of infection, postoperative transfusion, and new-onset atrial fibrillation were also found to be independently affected by 3-BG. Length of stay is also significantly related to 3-BG, by approximately 1 day for every 77-mg/dL increase.

In all, the Portland data thus far point to the need for change in current hospital practice. “It begs us to do something different, to not just report if a patient is diabetic or not,” Dr. Furnary commented.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, agreed. He summarized data from other recent studies of non-ICU populations that come to the same conclusion, including one of 1,253 patients with acute MI in whom in-hospital mortality did not differ between diabetic and nondiabetic patients, but was significantly greater among those with hyperglycemia on admission (defined as plasma glucose greater than 198 mg/dL) in both diabetic (10% vs. 5%) and nondiabetic (24% vs. 6%) patients (Am. Heart J. 2005;150:814–20).

According to Dr. Hirsch, two major trials published in 2005 that also support the same conclusion have been misinterpreted as negative. One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis showed that fasting blood glucose at baseline and during the study strongly predicted mortality (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

FORT LAUDERDALE, FLA. — Reduced responsiveness to repeat bisphosphonate treatment in patients with Paget's disease of bone appears to be limited to pamidronate and may not be a problem with the newer, more potent agents, Dr. Socrates Papapoulos said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

“The issue of bisphosphonate resistance does not appear to be of primary importance for our clinical practice, especially with the more potent agents now available,” said Dr. Papapoulos, professor of medicine and director of bone and mineral research at Leiden (the Netherlands) University Medical Center.

For most patients with Paget's disease of bone, short courses of bisphosphonate treatment typically result in remissions of 2 years or longer, and recurrences usually respond well to a new course of treatment. However, there have been reports of reduced responsiveness on repeat treatment. This so-called acquired resistance is characterized by a decrease in the magnitude of response, a need for higher doses to achieve the same response, and a shortening of the remission period compared with the initial treatment, he explained.

Previous literature on the subject has been confusing, particularly in the way responsiveness is measured. Some consider fractional decreases in serum alkaline phosphatase (AP) to be indicative of responsiveness, which is not valid because those values will almost always be lower on retreatment than at baseline, he said, adding that absolute serum AP values must be reported in order to assess the phenomenon of resistance.

To examine this issue, Dr. Papapoulos and his associates reviewed the records of 205 Paget's disease patients who had received two or more consecutive courses (up to nine courses) of either pamidronate or olpadronate. They received a total of 807 treatment courses with a mean follow-up per treatment of 29 months.

Overall, there was no difference in responsiveness—defined as a progressive increase in nadir serum AP—after initial versus subsequent treatment, nor was there a shorter period of remission following treatment. However, when the patients who had received only pamidronate were examined separately, there was a trend toward reduced responsiveness with pamidronate.

When the pamidronate patients were divided into those who had three or more affected bones versus those with two or fewer affected bones, the trend was seen only among those with more extensive disease. This finding is consistent with previous reports of acquired resistance to pamidronate in patients with extensive Paget's disease, Dr. Papapoulos noted.

FORT LAUDERDALE, FLA. — Reduced responsiveness to repeat bisphosphonate treatment in patients with Paget's disease of bone appears to be limited to pamidronate and may not be a problem with the newer, more potent agents, Dr. Socrates Papapoulos said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

“The issue of bisphosphonate resistance does not appear to be of primary importance for our clinical practice, especially with the more potent agents now available,” said Dr. Papapoulos, professor of medicine and director of bone and mineral research at Leiden (the Netherlands) University Medical Center.

For most patients with Paget's disease of bone, short courses of bisphosphonate treatment typically result in remissions of 2 years or longer, and recurrences usually respond well to a new course of treatment. However, there have been reports of reduced responsiveness on repeat treatment. This so-called acquired resistance is characterized by a decrease in the magnitude of response, a need for higher doses to achieve the same response, and a shortening of the remission period compared with the initial treatment, he explained.

Previous literature on the subject has been confusing, particularly in the way responsiveness is measured. Some consider fractional decreases in serum alkaline phosphatase (AP) to be indicative of responsiveness, which is not valid because those values will almost always be lower on retreatment than at baseline, he said, adding that absolute serum AP values must be reported in order to assess the phenomenon of resistance.

To examine this issue, Dr. Papapoulos and his associates reviewed the records of 205 Paget's disease patients who had received two or more consecutive courses (up to nine courses) of either pamidronate or olpadronate. They received a total of 807 treatment courses with a mean follow-up per treatment of 29 months.

Overall, there was no difference in responsiveness—defined as a progressive increase in nadir serum AP—after initial versus subsequent treatment, nor was there a shorter period of remission following treatment. However, when the patients who had received only pamidronate were examined separately, there was a trend toward reduced responsiveness with pamidronate.

When the pamidronate patients were divided into those who had three or more affected bones versus those with two or fewer affected bones, the trend was seen only among those with more extensive disease. This finding is consistent with previous reports of acquired resistance to pamidronate in patients with extensive Paget's disease, Dr. Papapoulos noted.

FORT LAUDERDALE, FLA. — Reduced responsiveness to repeat bisphosphonate treatment in patients with Paget's disease of bone appears to be limited to pamidronate and may not be a problem with the newer, more potent agents, Dr. Socrates Papapoulos said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

“The issue of bisphosphonate resistance does not appear to be of primary importance for our clinical practice, especially with the more potent agents now available,” said Dr. Papapoulos, professor of medicine and director of bone and mineral research at Leiden (the Netherlands) University Medical Center.

For most patients with Paget's disease of bone, short courses of bisphosphonate treatment typically result in remissions of 2 years or longer, and recurrences usually respond well to a new course of treatment. However, there have been reports of reduced responsiveness on repeat treatment. This so-called acquired resistance is characterized by a decrease in the magnitude of response, a need for higher doses to achieve the same response, and a shortening of the remission period compared with the initial treatment, he explained.

Previous literature on the subject has been confusing, particularly in the way responsiveness is measured. Some consider fractional decreases in serum alkaline phosphatase (AP) to be indicative of responsiveness, which is not valid because those values will almost always be lower on retreatment than at baseline, he said, adding that absolute serum AP values must be reported in order to assess the phenomenon of resistance.

To examine this issue, Dr. Papapoulos and his associates reviewed the records of 205 Paget's disease patients who had received two or more consecutive courses (up to nine courses) of either pamidronate or olpadronate. They received a total of 807 treatment courses with a mean follow-up per treatment of 29 months.

Overall, there was no difference in responsiveness—defined as a progressive increase in nadir serum AP—after initial versus subsequent treatment, nor was there a shorter period of remission following treatment. However, when the patients who had received only pamidronate were examined separately, there was a trend toward reduced responsiveness with pamidronate.

When the pamidronate patients were divided into those who had three or more affected bones versus those with two or fewer affected bones, the trend was seen only among those with more extensive disease. This finding is consistent with previous reports of acquired resistance to pamidronate in patients with extensive Paget's disease, Dr. Papapoulos noted.

FT. LAUDERDALE, FLA. — Bisphosphonate treatment is often extended beyond the duration recommended by the label in patients with Paget's disease of bone, Mohamed Omar, Ph.D., and his associates reported in a poster at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Paget's disease is the second most common bone disorder among elderly persons, after osteoporosis; about 70–90% of patients are asymptomatic and diagnoses are typically made from incidental findings of elevated lab values or radiographic abnormalities. Bisphosphonates are the standard treatment, said Dr. Omar, of Novartis Pharmaceuticals Corp., East Hanover, N.J., and his associates.

For patients diagnosed with the disease, risedronate therapy is recommended for 2 months and alendronate and etidronate for 6 months. After the recommended treatment course, patients should be evaluated to determine whether they need retreatment. Claims data from a large nationally representative health care database were reviewed for the years 1996–2004. At least one prescription for a bisphosphonate had been written for 433 Paget's disease patients (mean age 65 years, 64.3% female). None had osteoporosis, which would require ongoing bisphosphonate therapy. One-third (33.9%) had been prescribed by general practitioners/internists, followed by endocrinologists (12.5%) and rheumatologists (9.8%).

The most frequently prescribed bisphosphonates were alendronate (53%), followed by risedronate (35%) and etidronate (7%). Additional use, defined as receipt of medication after the recommended treatment regimen for each product's approved label, was most often seen with alendronate (45%), followed by risedronate (41%), and etidronate (18%).

Among the patients with additional use, those taking etidronate had the highest number of mean incremental days' supply (143), followed by risedronate (142), and alendronate (139). Incremental costs of those additional supplies were $995 for those on etidronate, $2,697 for risendronate, and $828 for alendronate, Dr. Omar noted. It's not clear whether increased use of drug therapy reflected a true need for retreatment or inappropriate prescribing, he said.

Novartis is the maker of zoledronic acid, a bisphosphonate under consideration by the Food and Drug Administration for the treatment of Paget's disease.

FT. LAUDERDALE, FLA. — Bisphosphonate treatment is often extended beyond the duration recommended by the label in patients with Paget's disease of bone, Mohamed Omar, Ph.D., and his associates reported in a poster at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Paget's disease is the second most common bone disorder among elderly persons, after osteoporosis; about 70–90% of patients are asymptomatic and diagnoses are typically made from incidental findings of elevated lab values or radiographic abnormalities. Bisphosphonates are the standard treatment, said Dr. Omar, of Novartis Pharmaceuticals Corp., East Hanover, N.J., and his associates.

For patients diagnosed with the disease, risedronate therapy is recommended for 2 months and alendronate and etidronate for 6 months. After the recommended treatment course, patients should be evaluated to determine whether they need retreatment. Claims data from a large nationally representative health care database were reviewed for the years 1996–2004. At least one prescription for a bisphosphonate had been written for 433 Paget's disease patients (mean age 65 years, 64.3% female). None had osteoporosis, which would require ongoing bisphosphonate therapy. One-third (33.9%) had been prescribed by general practitioners/internists, followed by endocrinologists (12.5%) and rheumatologists (9.8%).

The most frequently prescribed bisphosphonates were alendronate (53%), followed by risedronate (35%) and etidronate (7%). Additional use, defined as receipt of medication after the recommended treatment regimen for each product's approved label, was most often seen with alendronate (45%), followed by risedronate (41%), and etidronate (18%).

Among the patients with additional use, those taking etidronate had the highest number of mean incremental days' supply (143), followed by risedronate (142), and alendronate (139). Incremental costs of those additional supplies were $995 for those on etidronate, $2,697 for risendronate, and $828 for alendronate, Dr. Omar noted. It's not clear whether increased use of drug therapy reflected a true need for retreatment or inappropriate prescribing, he said.

Novartis is the maker of zoledronic acid, a bisphosphonate under consideration by the Food and Drug Administration for the treatment of Paget's disease.

FT. LAUDERDALE, FLA. — Bisphosphonate treatment is often extended beyond the duration recommended by the label in patients with Paget's disease of bone, Mohamed Omar, Ph.D., and his associates reported in a poster at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Paget's disease is the second most common bone disorder among elderly persons, after osteoporosis; about 70–90% of patients are asymptomatic and diagnoses are typically made from incidental findings of elevated lab values or radiographic abnormalities. Bisphosphonates are the standard treatment, said Dr. Omar, of Novartis Pharmaceuticals Corp., East Hanover, N.J., and his associates.

For patients diagnosed with the disease, risedronate therapy is recommended for 2 months and alendronate and etidronate for 6 months. After the recommended treatment course, patients should be evaluated to determine whether they need retreatment. Claims data from a large nationally representative health care database were reviewed for the years 1996–2004. At least one prescription for a bisphosphonate had been written for 433 Paget's disease patients (mean age 65 years, 64.3% female). None had osteoporosis, which would require ongoing bisphosphonate therapy. One-third (33.9%) had been prescribed by general practitioners/internists, followed by endocrinologists (12.5%) and rheumatologists (9.8%).

The most frequently prescribed bisphosphonates were alendronate (53%), followed by risedronate (35%) and etidronate (7%). Additional use, defined as receipt of medication after the recommended treatment regimen for each product's approved label, was most often seen with alendronate (45%), followed by risedronate (41%), and etidronate (18%).

Among the patients with additional use, those taking etidronate had the highest number of mean incremental days' supply (143), followed by risedronate (142), and alendronate (139). Incremental costs of those additional supplies were $995 for those on etidronate, $2,697 for risendronate, and $828 for alendronate, Dr. Omar noted. It's not clear whether increased use of drug therapy reflected a true need for retreatment or inappropriate prescribing, he said.

Novartis is the maker of zoledronic acid, a bisphosphonate under consideration by the Food and Drug Administration for the treatment of Paget's disease.

FORT LAUDERDALE, FLA. — The use of

In Paget's disease of bone, biochemical markers are used to monitor treatment response. But, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using

Twelve patients with monostotic Paget's disease underwent 1-hour dynamic

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he noted.

In response to a comment that PET scans are expensive, Dr. Devogelaer said, “We hope that the cost will decrease. But, we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT LAUDERDALE, FLA. — The use of

In Paget's disease of bone, biochemical markers are used to monitor treatment response. But, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using

Twelve patients with monostotic Paget's disease underwent 1-hour dynamic

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he noted.

In response to a comment that PET scans are expensive, Dr. Devogelaer said, “We hope that the cost will decrease. But, we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT LAUDERDALE, FLA. — The use of

In Paget's disease of bone, biochemical markers are used to monitor treatment response. But, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using

Twelve patients with monostotic Paget's disease underwent 1-hour dynamic

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he noted.

In response to a comment that PET scans are expensive, Dr. Devogelaer said, “We hope that the cost will decrease. But, we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT 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 study 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 vitamin D 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 of the year (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.

The initial idea for this investigation came from a patient seen in the metabolic bone clinic who had both hypovitaminosis D and documented active Paget's disease of the tibia with intense pain in the area.

The pain resolved completely when the patient's vitamin D deficiency was treated.

Aside from reducing musculoskeletal pain, other potential benefits of correcting hypovitaminosis D in patients with Paget's disease include ensuring that markers of bone turnover actually reflect Paget's disease activity, decreasing fracture risk, improving muscle strength and balance, and reducing the risks of both hypocalcemia and osteomalacic new bone formation resulting from bisphosphonate treatment, Dr. Kelly and Dr. Moses said.

FORT 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 study 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 vitamin D 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 of the year (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.

The initial idea for this investigation came from a patient seen in the metabolic bone clinic who had both hypovitaminosis D and documented active Paget's disease of the tibia with intense pain in the area.

The pain resolved completely when the patient's vitamin D deficiency was treated.

Aside from reducing musculoskeletal pain, other potential benefits of correcting hypovitaminosis D in patients with Paget's disease include ensuring that markers of bone turnover actually reflect Paget's disease activity, decreasing fracture risk, improving muscle strength and balance, and reducing the risks of both hypocalcemia and osteomalacic new bone formation resulting from bisphosphonate treatment, Dr. Kelly and Dr. Moses said.

FORT 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 study 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 vitamin D 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 of the year (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.

The initial idea for this investigation came from a patient seen in the metabolic bone clinic who had both hypovitaminosis D and documented active Paget's disease of the tibia with intense pain in the area.

The pain resolved completely when the patient's vitamin D deficiency was treated.

Aside from reducing musculoskeletal pain, other potential benefits of correcting hypovitaminosis D in patients with Paget's disease include ensuring that markers of bone turnover actually reflect Paget's disease activity, decreasing fracture risk, improving muscle strength and balance, and reducing the risks of both hypocalcemia and osteomalacic new bone formation resulting from bisphosphonate treatment, Dr. Kelly and Dr. Moses said.

FORT 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 of bone 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. Hypercalcemia and hypercalciuria, only occasional findings in Paget's disease, are commonly seen in hyperparathyroidism. Malignant bone tumors are present in up to 1% of Paget's disease patients but are rare in hyperparathyroidism, 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.

Secondary hyperparathyroidism can also result directly from the increased bone turnover in Paget's disease—a consequence of increased calcium demands during periods of pagetic bone formation—or from bisphosphonate treatment. Dietary supplementation with calcium and vitamin D can protect against this problem in patients undergoing bisphosphonate treatment, she said.

FORT 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 of bone 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. Hypercalcemia and hypercalciuria, only occasional findings in Paget's disease, are commonly seen in hyperparathyroidism. Malignant bone tumors are present in up to 1% of Paget's disease patients but are rare in hyperparathyroidism, 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.

Secondary hyperparathyroidism can also result directly from the increased bone turnover in Paget's disease—a consequence of increased calcium demands during periods of pagetic bone formation—or from bisphosphonate treatment. Dietary supplementation with calcium and vitamin D can protect against this problem in patients undergoing bisphosphonate treatment, she said.

FORT 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 of bone 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. Hypercalcemia and hypercalciuria, only occasional findings in Paget's disease, are commonly seen in hyperparathyroidism. Malignant bone tumors are present in up to 1% of Paget's disease patients but are rare in hyperparathyroidism, 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.

Secondary hyperparathyroidism can also result directly from the increased bone turnover in Paget's disease—a consequence of increased calcium demands during periods of pagetic bone formation—or from bisphosphonate treatment. Dietary supplementation with calcium and vitamin D can protect against this problem in patients undergoing bisphosphonate treatment, she said.

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the ongoing Portland Diabetic Project, a prospective, nonrandomized interventional study of the relation between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards.

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first, the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, said Dr. Furnary. Mortality in CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality in nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% in diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, said two major trials published in 2005 supporting the same conclusion have been misinterpreted as negative.

One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis confirmed that fasting blood glucose at baseline and during the study strongly predicted mortality, with an odds ratio of 1.20 (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

Finally, a national sample of 141,680 elderly patients with acute MI showed that at least patients who are known to have diabetes seem to be receiving more aggressive care than in years past. On admission, 30% had documented diabetes, whereas substantial proportions of those who entered with elevated glucose did not have that diagnosis.

While in the hospital, 73% of diabetic patients who came in with a glucose level above 240 mg/dL were treated with insulin, compared with 22% of those with the same level of hyperglycemia who did not have the diabetes diagnosis. Though 30-day and 1-year mortality increased with higher glucose levels at admission in both groups, the effect was much greater in those without known diabetes: For them, the increased mortality began at values of 110 mg/dL, while in the diabetic group the difference in mortality was seen only in those with admission glucose levels above 240 mg/dL (Circulation 2005;111:3078–86).

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the ongoing Portland Diabetic Project, a prospective, nonrandomized interventional study of the relation between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards.

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first, the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, said Dr. Furnary. Mortality in CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality in nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% in diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, said two major trials published in 2005 supporting the same conclusion have been misinterpreted as negative.

One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis confirmed that fasting blood glucose at baseline and during the study strongly predicted mortality, with an odds ratio of 1.20 (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

Finally, a national sample of 141,680 elderly patients with acute MI showed that at least patients who are known to have diabetes seem to be receiving more aggressive care than in years past. On admission, 30% had documented diabetes, whereas substantial proportions of those who entered with elevated glucose did not have that diagnosis.

While in the hospital, 73% of diabetic patients who came in with a glucose level above 240 mg/dL were treated with insulin, compared with 22% of those with the same level of hyperglycemia who did not have the diabetes diagnosis. Though 30-day and 1-year mortality increased with higher glucose levels at admission in both groups, the effect was much greater in those without known diabetes: For them, the increased mortality began at values of 110 mg/dL, while in the diabetic group the difference in mortality was seen only in those with admission glucose levels above 240 mg/dL (Circulation 2005;111:3078–86).

WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association.

In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.

“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.

He presented the latest data from the ongoing Portland Diabetic Project, a prospective, nonrandomized interventional study of the relation between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards.

Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.

Glucose targets for the insulin infusion protocol have been ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first, the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.

During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.

In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, said Dr. Furnary. Mortality in CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality in nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% in diabetic CABG patients nationwide, he said.

Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value.

Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, said two major trials published in 2005 supporting the same conclusion have been misinterpreted as negative.

One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis confirmed that fasting blood glucose at baseline and during the study strongly predicted mortality, with an odds ratio of 1.20 (Euro. Heart J. 2005;26:650–61).

In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).

Finally, a national sample of 141,680 elderly patients with acute MI showed that at least patients who are known to have diabetes seem to be receiving more aggressive care than in years past. On admission, 30% had documented diabetes, whereas substantial proportions of those who entered with elevated glucose did not have that diagnosis.

While in the hospital, 73% of diabetic patients who came in with a glucose level above 240 mg/dL were treated with insulin, compared with 22% of those with the same level of hyperglycemia who did not have the diabetes diagnosis. Though 30-day and 1-year mortality increased with higher glucose levels at admission in both groups, the effect was much greater in those without known diabetes: For them, the increased mortality began at values of 110 mg/dL, while in the diabetic group the difference in mortality was seen only in those with admission glucose levels above 240 mg/dL (Circulation 2005;111:3078–86).