Diana Mahoney

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News

Angiotensin-receptor II blockers are associated with a modestly increased risk of new cancer diagnoses according to a meta-analysis of randomized controlled trials.

The limited amount of new cancer data in the available literature, however, precludes the calculation of exact cancer risk associated with each individual agent in this class of drugs, wrote lead investigator Dr. Ilke Sipahi and colleagues at Case Western Reserve University in Cleveland.

Angiotensin receptor II blockers (ARBs) are commonly used for the treatment of hypertension, heart failure, and diabetic neuropathy. Because a number of large ARB trials have been completed since 2003, when “an unexpected finding” of significantly higher fatal cancers among patients taking the ARB candesartan was observed in a study assessing the efficacy of the drug in heart failure (Lancet 2003;362:759-66), Dr. Sipahi and his colleagues designed a meta-analysis of the published randomized controlled trials drugs in this class to examine their effect on the occurrence of new cancers. Secondary objectives included the determination of whether ARBs are associated with the occurrence of specific solid-organ cancers and cancer deaths, they wrote.

The meta-analysis included studies published before November 2009 in which an ARB was given in at least one group. Only those studies that enrolled least 100 patients and had a minimum 1 year follow-up were considered, according to the authors. Of the trials that fit these criteria and reported cancer data, five (61,590 patients) had new-cancer data available and were included for the evaluation of the primary outcome of new cancer occurrence. Additionally, for consideration of the secondary outcomes, five trials that reported data on common types of solid organ cancers (68,402 patients) and eight trials that reported data on cancer deaths (93,515) were evaluated, the authors wrote, noting that nine trials were included overall (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-6]).

For the primary outcome of cancer recurrence, patients who were randomized to ARB treatment had 7.2% risk of new cancer occurrence compared with a 6.0% risk among patients in the control groups, which is a statistically significant increase, the authors reported. An analysis of three of the trials in which cancer was a prespecified end point and cancer data was rigorously collected also showed a significant increase in risk of cancer with ARBs, they wrote.

Because the ARB telmisartan was used as the study drug in 86% of the patients randomized to an ARB, the investigators conducted a meta-analysis of three of the trials looking at this drug showed an increase in new cancer occurrence of borderline significance. Analyses looking specifically at patients on background ACE inhibitor therapy and looking at patients without concomitant ACE inhibitor treatment also showed significant increases in new cancer occurrences, they reported.

For the secondary outcome of the occurrence of specific solid organ cancers, the “meta-analysis showed an increase in relative risk for the occurrence of new lung cancer in patients randomized to an ARB compared with control,” the authors wrote. “This effect was also seen in the subgroup of patients who received background ACE-inhibitor therapy.” While there was an excess of prostate cancer in the ARB groups in all five trials, it was not significant in meta-analysis, they stated.

When evaluating for cancer deaths, the authors wrote “there was no significant difference in cancer deaths between patients randomized to ARBs and those randomized to control for the duration of the follow-up.”

The clinical significance of the “modest but significant” increased risk of new cancer occurrence is unknown, the authors conceded. “The finding of a 1.2% increase in absolute risk of cancer over an average of 4 years needs to be interpreted in view of the estimated 41% lifetime cancer risk,” they wrote.

Importantly, because new cancer data were available for only three of seven FDA-approved ARBs, and because most of the patients included in the meta-analysis received telmisartan, “it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug,” the authors stated, nor is it known whether the remaining four ARBs are associated with an increased risk of new cancers.

The mechanism for the possible increase in new cancer occurrences associated with ARBs is uncertain, according the authors. Although experimental studies using cancer cell lines and mouse models have implicated the renin-angiotensin system in the regulation of cell proliferation, tumor growth, angiogenesis, and metastasis, and evidence shows that both angiotensin II type-1 blockade with ARB and direct stimulation of angiotensin II type-2 are capable of stimulating tumor angiogenesis in vivo, the authors wrote, “the relevance of these observations in human malignancy is largely unknown.”

Although the findings of this study are limited by the fact that the pooled results come from trials not designed to explore cancer outcomes as the primary end point and by the lack of individual patient-level cancer data, “meta-analysis can be useful in providing insights into issues of safety and rare adverse events that might provide the hypothesis for a prospective trial,” the authors wrote, noting that the findings “warrant further investigation.”

My Take

This Raises Crucial Safety Questions

The meta-analysis linking angiotensin receptor blockers with an increased risk of incident cancer raises crucial drug safety questions. “Are angiotensin-receptor blockers associated with increased risk of incident malignancies? Should we be concerned about all ARBs or a single drug, telmisartan? How can this uncertainty best be resolved? What actions should practitioners take while this concern undergoes further examination and analysis?”

While the meta-analysis has its strengths—particularly its size, the thoroughness of the literature search, and the application of appropriate filters to exclude potentially unreliable data, “there are also important weaknesses, which the investigators acknowledge—including the post hoc nature of this investigation and the fact that the trials were not designed to explore cancer outcomes,” leading the investigators to be “appropriately cautious” in their interpretation of the data.

Until regulators review the possible association between ARB use and cancer and report their findings, “we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme inhibitors. ARBs can be reserved for patients with intolerance to ACE inhibitors.” Using ARBs more selectively will also save money, “since nearly all ARBs are proprietary while ACE inhibitors are generic.”

STEVEN E. NISSEN, M.D., is chair of the department of cardiovascular medicine at the Cleveland Clinic. His remarks were made in an editorial (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-X]). He has received research support from Pfizer, Astra Zeneca, Novartis, Novo Nordisk Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly. He consults for many pharmaceutical companies, but donates all related money to charity.

Vitals

Angiotensin-receptor II blockers are associated with a modestly increased risk of new cancer diagnoses according to a meta-analysis of randomized controlled trials.

The limited amount of new cancer data in the available literature, however, precludes the calculation of exact cancer risk associated with each individual agent in this class of drugs, wrote lead investigator Dr. Ilke Sipahi and colleagues at Case Western Reserve University in Cleveland.

Angiotensin receptor II blockers (ARBs) are commonly used for the treatment of hypertension, heart failure, and diabetic neuropathy. Because a number of large ARB trials have been completed since 2003, when “an unexpected finding” of significantly higher fatal cancers among patients taking the ARB candesartan was observed in a study assessing the efficacy of the drug in heart failure (Lancet 2003;362:759-66), Dr. Sipahi and his colleagues designed a meta-analysis of the published randomized controlled trials drugs in this class to examine their effect on the occurrence of new cancers. Secondary objectives included the determination of whether ARBs are associated with the occurrence of specific solid-organ cancers and cancer deaths, they wrote.

The meta-analysis included studies published before November 2009 in which an ARB was given in at least one group. Only those studies that enrolled least 100 patients and had a minimum 1 year follow-up were considered, according to the authors. Of the trials that fit these criteria and reported cancer data, five (61,590 patients) had new-cancer data available and were included for the evaluation of the primary outcome of new cancer occurrence. Additionally, for consideration of the secondary outcomes, five trials that reported data on common types of solid organ cancers (68,402 patients) and eight trials that reported data on cancer deaths (93,515) were evaluated, the authors wrote, noting that nine trials were included overall (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-6]).

For the primary outcome of cancer recurrence, patients who were randomized to ARB treatment had 7.2% risk of new cancer occurrence compared with a 6.0% risk among patients in the control groups, which is a statistically significant increase, the authors reported. An analysis of three of the trials in which cancer was a prespecified end point and cancer data was rigorously collected also showed a significant increase in risk of cancer with ARBs, they wrote.

Because the ARB telmisartan was used as the study drug in 86% of the patients randomized to an ARB, the investigators conducted a meta-analysis of three of the trials looking at this drug showed an increase in new cancer occurrence of borderline significance. Analyses looking specifically at patients on background ACE inhibitor therapy and looking at patients without concomitant ACE inhibitor treatment also showed significant increases in new cancer occurrences, they reported.

For the secondary outcome of the occurrence of specific solid organ cancers, the “meta-analysis showed an increase in relative risk for the occurrence of new lung cancer in patients randomized to an ARB compared with control,” the authors wrote. “This effect was also seen in the subgroup of patients who received background ACE-inhibitor therapy.” While there was an excess of prostate cancer in the ARB groups in all five trials, it was not significant in meta-analysis, they stated.

When evaluating for cancer deaths, the authors wrote “there was no significant difference in cancer deaths between patients randomized to ARBs and those randomized to control for the duration of the follow-up.”

The clinical significance of the “modest but significant” increased risk of new cancer occurrence is unknown, the authors conceded. “The finding of a 1.2% increase in absolute risk of cancer over an average of 4 years needs to be interpreted in view of the estimated 41% lifetime cancer risk,” they wrote.

Importantly, because new cancer data were available for only three of seven FDA-approved ARBs, and because most of the patients included in the meta-analysis received telmisartan, “it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug,” the authors stated, nor is it known whether the remaining four ARBs are associated with an increased risk of new cancers.

The mechanism for the possible increase in new cancer occurrences associated with ARBs is uncertain, according the authors. Although experimental studies using cancer cell lines and mouse models have implicated the renin-angiotensin system in the regulation of cell proliferation, tumor growth, angiogenesis, and metastasis, and evidence shows that both angiotensin II type-1 blockade with ARB and direct stimulation of angiotensin II type-2 are capable of stimulating tumor angiogenesis in vivo, the authors wrote, “the relevance of these observations in human malignancy is largely unknown.”

Although the findings of this study are limited by the fact that the pooled results come from trials not designed to explore cancer outcomes as the primary end point and by the lack of individual patient-level cancer data, “meta-analysis can be useful in providing insights into issues of safety and rare adverse events that might provide the hypothesis for a prospective trial,” the authors wrote, noting that the findings “warrant further investigation.”

My Take

This Raises Crucial Safety Questions

The meta-analysis linking angiotensin receptor blockers with an increased risk of incident cancer raises crucial drug safety questions. “Are angiotensin-receptor blockers associated with increased risk of incident malignancies? Should we be concerned about all ARBs or a single drug, telmisartan? How can this uncertainty best be resolved? What actions should practitioners take while this concern undergoes further examination and analysis?”

While the meta-analysis has its strengths—particularly its size, the thoroughness of the literature search, and the application of appropriate filters to exclude potentially unreliable data, “there are also important weaknesses, which the investigators acknowledge—including the post hoc nature of this investigation and the fact that the trials were not designed to explore cancer outcomes,” leading the investigators to be “appropriately cautious” in their interpretation of the data.

Until regulators review the possible association between ARB use and cancer and report their findings, “we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme inhibitors. ARBs can be reserved for patients with intolerance to ACE inhibitors.” Using ARBs more selectively will also save money, “since nearly all ARBs are proprietary while ACE inhibitors are generic.”

STEVEN E. NISSEN, M.D., is chair of the department of cardiovascular medicine at the Cleveland Clinic. His remarks were made in an editorial (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-X]). He has received research support from Pfizer, Astra Zeneca, Novartis, Novo Nordisk Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly. He consults for many pharmaceutical companies, but donates all related money to charity.

Vitals

Angiotensin-receptor II blockers are associated with a modestly increased risk of new cancer diagnoses according to a meta-analysis of randomized controlled trials.

The limited amount of new cancer data in the available literature, however, precludes the calculation of exact cancer risk associated with each individual agent in this class of drugs, wrote lead investigator Dr. Ilke Sipahi and colleagues at Case Western Reserve University in Cleveland.

Angiotensin receptor II blockers (ARBs) are commonly used for the treatment of hypertension, heart failure, and diabetic neuropathy. Because a number of large ARB trials have been completed since 2003, when “an unexpected finding” of significantly higher fatal cancers among patients taking the ARB candesartan was observed in a study assessing the efficacy of the drug in heart failure (Lancet 2003;362:759-66), Dr. Sipahi and his colleagues designed a meta-analysis of the published randomized controlled trials drugs in this class to examine their effect on the occurrence of new cancers. Secondary objectives included the determination of whether ARBs are associated with the occurrence of specific solid-organ cancers and cancer deaths, they wrote.

The meta-analysis included studies published before November 2009 in which an ARB was given in at least one group. Only those studies that enrolled least 100 patients and had a minimum 1 year follow-up were considered, according to the authors. Of the trials that fit these criteria and reported cancer data, five (61,590 patients) had new-cancer data available and were included for the evaluation of the primary outcome of new cancer occurrence. Additionally, for consideration of the secondary outcomes, five trials that reported data on common types of solid organ cancers (68,402 patients) and eight trials that reported data on cancer deaths (93,515) were evaluated, the authors wrote, noting that nine trials were included overall (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-6]).

For the primary outcome of cancer recurrence, patients who were randomized to ARB treatment had 7.2% risk of new cancer occurrence compared with a 6.0% risk among patients in the control groups, which is a statistically significant increase, the authors reported. An analysis of three of the trials in which cancer was a prespecified end point and cancer data was rigorously collected also showed a significant increase in risk of cancer with ARBs, they wrote.

Because the ARB telmisartan was used as the study drug in 86% of the patients randomized to an ARB, the investigators conducted a meta-analysis of three of the trials looking at this drug showed an increase in new cancer occurrence of borderline significance. Analyses looking specifically at patients on background ACE inhibitor therapy and looking at patients without concomitant ACE inhibitor treatment also showed significant increases in new cancer occurrences, they reported.

For the secondary outcome of the occurrence of specific solid organ cancers, the “meta-analysis showed an increase in relative risk for the occurrence of new lung cancer in patients randomized to an ARB compared with control,” the authors wrote. “This effect was also seen in the subgroup of patients who received background ACE-inhibitor therapy.” While there was an excess of prostate cancer in the ARB groups in all five trials, it was not significant in meta-analysis, they stated.

When evaluating for cancer deaths, the authors wrote “there was no significant difference in cancer deaths between patients randomized to ARBs and those randomized to control for the duration of the follow-up.”

The clinical significance of the “modest but significant” increased risk of new cancer occurrence is unknown, the authors conceded. “The finding of a 1.2% increase in absolute risk of cancer over an average of 4 years needs to be interpreted in view of the estimated 41% lifetime cancer risk,” they wrote.

Importantly, because new cancer data were available for only three of seven FDA-approved ARBs, and because most of the patients included in the meta-analysis received telmisartan, “it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug,” the authors stated, nor is it known whether the remaining four ARBs are associated with an increased risk of new cancers.

The mechanism for the possible increase in new cancer occurrences associated with ARBs is uncertain, according the authors. Although experimental studies using cancer cell lines and mouse models have implicated the renin-angiotensin system in the regulation of cell proliferation, tumor growth, angiogenesis, and metastasis, and evidence shows that both angiotensin II type-1 blockade with ARB and direct stimulation of angiotensin II type-2 are capable of stimulating tumor angiogenesis in vivo, the authors wrote, “the relevance of these observations in human malignancy is largely unknown.”

Although the findings of this study are limited by the fact that the pooled results come from trials not designed to explore cancer outcomes as the primary end point and by the lack of individual patient-level cancer data, “meta-analysis can be useful in providing insights into issues of safety and rare adverse events that might provide the hypothesis for a prospective trial,” the authors wrote, noting that the findings “warrant further investigation.”

My Take

This Raises Crucial Safety Questions

The meta-analysis linking angiotensin receptor blockers with an increased risk of incident cancer raises crucial drug safety questions. “Are angiotensin-receptor blockers associated with increased risk of incident malignancies? Should we be concerned about all ARBs or a single drug, telmisartan? How can this uncertainty best be resolved? What actions should practitioners take while this concern undergoes further examination and analysis?”

While the meta-analysis has its strengths—particularly its size, the thoroughness of the literature search, and the application of appropriate filters to exclude potentially unreliable data, “there are also important weaknesses, which the investigators acknowledge—including the post hoc nature of this investigation and the fact that the trials were not designed to explore cancer outcomes,” leading the investigators to be “appropriately cautious” in their interpretation of the data.

Until regulators review the possible association between ARB use and cancer and report their findings, “we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme inhibitors. ARBs can be reserved for patients with intolerance to ACE inhibitors.” Using ARBs more selectively will also save money, “since nearly all ARBs are proprietary while ACE inhibitors are generic.”

STEVEN E. NISSEN, M.D., is chair of the department of cardiovascular medicine at the Cleveland Clinic. His remarks were made in an editorial (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-X]). He has received research support from Pfizer, Astra Zeneca, Novartis, Novo Nordisk Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly. He consults for many pharmaceutical companies, but donates all related money to charity.

Vitals

Immunization with common vaccines is not associated with an increased risk for rheumatoid arthritis, nor does it trigger the autoimmune disease in individuals who have established risk factors, according to an analysis of data that was presented by Camilla Bengtsson at the annual European Congress of Rheumatology on June 16.

Although anecdotal reports have suggested that common vaccinations might be inciting agents for rheumatoid arthritis, no sufficiently powered epidemiologic studies have addressed this concern, according to Ms. Bengtsson, a doctoral candidate at the Karolinska Institute in Stockholm.

Using data on 1,851 people with RA from the Swedish population-based EIRA (Epidemiological Investigation of Rheumatoid Arthritis) data set and 1,984 healthy matched controls, Ms. Bengtsson and her associates investigated the possible association between vaccinations that are commonly used in industrialized societies (influenza; tetanus; diphtheria; tick-borne encephalitis; hepatitis A, B, and C; polio; and pneumococcus) and the risk for RA, as well as the impact of vaccinations on two subsets of RA patients: those with and without antibodies to citrullinated peptides. Ms. Bengtsson discussed their findings on potential interactions between vaccination and smoking and between vaccination and the presence of HLA-DRB1 SE alleles with respect to RA risk, both of which have been implicated anecdotally as possible catalysts for the disease.

To evaluate these potential associations, the investigators compared the 582 individuals in the EIRA data set who had been vaccinated in the 5 years prior to disease onset with the 1,269 RA patients who had not been vaccinated within 5 years prior to disease onset. Among the control subjects, 617 had been vaccinated and 1,367 had not been vaccinated within the preceding 5 years.

Vaccine by vaccine, the odds ratio for developing RA after influenza vaccination was 1.1 (252 RA patients and 279 controls had received the flu vaccine during the period of interest). The OR for RA after tetanus vaccination was 1.0 (170 cases and 179 controls had received that vaccination). The OR was 1.0 for diphtheria vaccination (71 cases/71 controls). For tick-borne encephalitis, the OR was 0.8 (91 cases/122 controls). The OR for hepatitis A, B, and C was 0.9 (105 cases/124 controls). The OR for polio vaccination was 1.1 (29 cases/31 controls). The OR for pneumococcus was 1.0 (22 cases/22 controls). The RA OR for the unvaccinated was 1.0 (1,269 cases/1,367 controls).

There was no statistically significant difference among the outcomes. Based on the analysis, vaccinations did not increase the risk of RA overall. Being negative or positive for antibodies to citrullinated peptides did not alter the risk for RA among the vaccinated or unvaccinated subjects, according to Ms. Bengtsson. Additionally, there was no association between any specific vaccine and the risk of RA, nor did vaccinations increase the risk of RA among smokers or among carriers of HLA-DRB1 SE alleles, she said.

The results indicate that “immunological provocation with common vaccines given to adults in their present form is not a major risk factor for RA, at least not vaccines administered [within 5 years] before onset of disease,” Ms. Bengtsson noted, suggesting that clinicians point to these findings to encourage patients to follow recommended immunization guidelines.

No conflicts of interest were reported.

Immunization with common vaccines is not associated with an increased risk for rheumatoid arthritis, nor does it trigger the autoimmune disease in individuals who have established risk factors, according to an analysis of data that was presented by Camilla Bengtsson at the annual European Congress of Rheumatology on June 16.

Although anecdotal reports have suggested that common vaccinations might be inciting agents for rheumatoid arthritis, no sufficiently powered epidemiologic studies have addressed this concern, according to Ms. Bengtsson, a doctoral candidate at the Karolinska Institute in Stockholm.

Using data on 1,851 people with RA from the Swedish population-based EIRA (Epidemiological Investigation of Rheumatoid Arthritis) data set and 1,984 healthy matched controls, Ms. Bengtsson and her associates investigated the possible association between vaccinations that are commonly used in industrialized societies (influenza; tetanus; diphtheria; tick-borne encephalitis; hepatitis A, B, and C; polio; and pneumococcus) and the risk for RA, as well as the impact of vaccinations on two subsets of RA patients: those with and without antibodies to citrullinated peptides. Ms. Bengtsson discussed their findings on potential interactions between vaccination and smoking and between vaccination and the presence of HLA-DRB1 SE alleles with respect to RA risk, both of which have been implicated anecdotally as possible catalysts for the disease.

To evaluate these potential associations, the investigators compared the 582 individuals in the EIRA data set who had been vaccinated in the 5 years prior to disease onset with the 1,269 RA patients who had not been vaccinated within 5 years prior to disease onset. Among the control subjects, 617 had been vaccinated and 1,367 had not been vaccinated within the preceding 5 years.

Vaccine by vaccine, the odds ratio for developing RA after influenza vaccination was 1.1 (252 RA patients and 279 controls had received the flu vaccine during the period of interest). The OR for RA after tetanus vaccination was 1.0 (170 cases and 179 controls had received that vaccination). The OR was 1.0 for diphtheria vaccination (71 cases/71 controls). For tick-borne encephalitis, the OR was 0.8 (91 cases/122 controls). The OR for hepatitis A, B, and C was 0.9 (105 cases/124 controls). The OR for polio vaccination was 1.1 (29 cases/31 controls). The OR for pneumococcus was 1.0 (22 cases/22 controls). The RA OR for the unvaccinated was 1.0 (1,269 cases/1,367 controls).

There was no statistically significant difference among the outcomes. Based on the analysis, vaccinations did not increase the risk of RA overall. Being negative or positive for antibodies to citrullinated peptides did not alter the risk for RA among the vaccinated or unvaccinated subjects, according to Ms. Bengtsson. Additionally, there was no association between any specific vaccine and the risk of RA, nor did vaccinations increase the risk of RA among smokers or among carriers of HLA-DRB1 SE alleles, she said.

The results indicate that “immunological provocation with common vaccines given to adults in their present form is not a major risk factor for RA, at least not vaccines administered [within 5 years] before onset of disease,” Ms. Bengtsson noted, suggesting that clinicians point to these findings to encourage patients to follow recommended immunization guidelines.

No conflicts of interest were reported.

Immunization with common vaccines is not associated with an increased risk for rheumatoid arthritis, nor does it trigger the autoimmune disease in individuals who have established risk factors, according to an analysis of data that was presented by Camilla Bengtsson at the annual European Congress of Rheumatology on June 16.

Although anecdotal reports have suggested that common vaccinations might be inciting agents for rheumatoid arthritis, no sufficiently powered epidemiologic studies have addressed this concern, according to Ms. Bengtsson, a doctoral candidate at the Karolinska Institute in Stockholm.

Using data on 1,851 people with RA from the Swedish population-based EIRA (Epidemiological Investigation of Rheumatoid Arthritis) data set and 1,984 healthy matched controls, Ms. Bengtsson and her associates investigated the possible association between vaccinations that are commonly used in industrialized societies (influenza; tetanus; diphtheria; tick-borne encephalitis; hepatitis A, B, and C; polio; and pneumococcus) and the risk for RA, as well as the impact of vaccinations on two subsets of RA patients: those with and without antibodies to citrullinated peptides. Ms. Bengtsson discussed their findings on potential interactions between vaccination and smoking and between vaccination and the presence of HLA-DRB1 SE alleles with respect to RA risk, both of which have been implicated anecdotally as possible catalysts for the disease.

To evaluate these potential associations, the investigators compared the 582 individuals in the EIRA data set who had been vaccinated in the 5 years prior to disease onset with the 1,269 RA patients who had not been vaccinated within 5 years prior to disease onset. Among the control subjects, 617 had been vaccinated and 1,367 had not been vaccinated within the preceding 5 years.

Vaccine by vaccine, the odds ratio for developing RA after influenza vaccination was 1.1 (252 RA patients and 279 controls had received the flu vaccine during the period of interest). The OR for RA after tetanus vaccination was 1.0 (170 cases and 179 controls had received that vaccination). The OR was 1.0 for diphtheria vaccination (71 cases/71 controls). For tick-borne encephalitis, the OR was 0.8 (91 cases/122 controls). The OR for hepatitis A, B, and C was 0.9 (105 cases/124 controls). The OR for polio vaccination was 1.1 (29 cases/31 controls). The OR for pneumococcus was 1.0 (22 cases/22 controls). The RA OR for the unvaccinated was 1.0 (1,269 cases/1,367 controls).

There was no statistically significant difference among the outcomes. Based on the analysis, vaccinations did not increase the risk of RA overall. Being negative or positive for antibodies to citrullinated peptides did not alter the risk for RA among the vaccinated or unvaccinated subjects, according to Ms. Bengtsson. Additionally, there was no association between any specific vaccine and the risk of RA, nor did vaccinations increase the risk of RA among smokers or among carriers of HLA-DRB1 SE alleles, she said.

The results indicate that “immunological provocation with common vaccines given to adults in their present form is not a major risk factor for RA, at least not vaccines administered [within 5 years] before onset of disease,” Ms. Bengtsson noted, suggesting that clinicians point to these findings to encourage patients to follow recommended immunization guidelines.

No conflicts of interest were reported.

The breakthrough fully human monoclonal antibody denosumab (Prolia) received Food and Drug Administration approval for the treatment of postmenopausal osteoporosis following the agency's fast-track review and request for resubmission of data.

The approval is based primarily on the findings of a pivotal phase III clinical trial designed and funded by the drug manufacturer (Amgen), in which denosumab treatment was associated with a reduction in vertebral, nonvertebral, and hip fracture risk in women with osteoporosis.

Specifically, of the 7,808 women with osteoporosis between the ages of 60 and 90 years enrolled in the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial, those who were assigned to receive twice yearly injections of 60 mg denosumab for 3 years were 68% less likely to develop a vertebral fracture and 40% less likely to develop a hip fracture than were women in the placebo group. Additionally, significantly increased bone mineral density was observed at all of the key sites measured.

By targeting the receptor activator of nuclear factor-kappaB ligand (RANKL), which is the primary mediator of osteoclast formation, denosumab blocks the production of the bone-destroying osteoclasts and by so doing improves the density, volume, and strength of both cortical and trabecular bone, according to the authors (N. Engl. J. Med. 2009;361:756–65).

Among the side effects reported in the FREEDOM and other clinical trials of denosumab, the most common include back pain, musculoskeletal pain, extremity pain, hypercholesterolemia, and urinary and bladder infections, according to a statement issued by the FDA. Serious adverse reactions include hypercalcemia, dermatologic conditions, and infections.

The significance of the long-term suppression of bone remodeling is unknown, according to a press release issued by Amgen.

“The long-term consequences of the degree of suppression of bone remodeling observed with [denosumab] may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing,” the release stated, warning that patients should be monitored for these adverse outcomes.

The FDA approval of denosumab includes a risk evaluation and mitigation strategy comprising a medication guide for patients and communications to health care providers explaining the risks and benefits of the drug.

The approval of denosumab was delayed in October 2009, when the FDA's Division of Reproductive and Urologic Products issued a Complete Response Letter for the biologics license application for denosumab in the treatment and prevention of postmenopausal osteoporosis, according to Amgen.

The breakthrough fully human monoclonal antibody denosumab (Prolia) received Food and Drug Administration approval for the treatment of postmenopausal osteoporosis following the agency's fast-track review and request for resubmission of data.

The approval is based primarily on the findings of a pivotal phase III clinical trial designed and funded by the drug manufacturer (Amgen), in which denosumab treatment was associated with a reduction in vertebral, nonvertebral, and hip fracture risk in women with osteoporosis.

Specifically, of the 7,808 women with osteoporosis between the ages of 60 and 90 years enrolled in the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial, those who were assigned to receive twice yearly injections of 60 mg denosumab for 3 years were 68% less likely to develop a vertebral fracture and 40% less likely to develop a hip fracture than were women in the placebo group. Additionally, significantly increased bone mineral density was observed at all of the key sites measured.

By targeting the receptor activator of nuclear factor-kappaB ligand (RANKL), which is the primary mediator of osteoclast formation, denosumab blocks the production of the bone-destroying osteoclasts and by so doing improves the density, volume, and strength of both cortical and trabecular bone, according to the authors (N. Engl. J. Med. 2009;361:756–65).

Among the side effects reported in the FREEDOM and other clinical trials of denosumab, the most common include back pain, musculoskeletal pain, extremity pain, hypercholesterolemia, and urinary and bladder infections, according to a statement issued by the FDA. Serious adverse reactions include hypercalcemia, dermatologic conditions, and infections.

The significance of the long-term suppression of bone remodeling is unknown, according to a press release issued by Amgen.

“The long-term consequences of the degree of suppression of bone remodeling observed with [denosumab] may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing,” the release stated, warning that patients should be monitored for these adverse outcomes.

The FDA approval of denosumab includes a risk evaluation and mitigation strategy comprising a medication guide for patients and communications to health care providers explaining the risks and benefits of the drug.

The approval of denosumab was delayed in October 2009, when the FDA's Division of Reproductive and Urologic Products issued a Complete Response Letter for the biologics license application for denosumab in the treatment and prevention of postmenopausal osteoporosis, according to Amgen.

The breakthrough fully human monoclonal antibody denosumab (Prolia) received Food and Drug Administration approval for the treatment of postmenopausal osteoporosis following the agency's fast-track review and request for resubmission of data.

The approval is based primarily on the findings of a pivotal phase III clinical trial designed and funded by the drug manufacturer (Amgen), in which denosumab treatment was associated with a reduction in vertebral, nonvertebral, and hip fracture risk in women with osteoporosis.

Specifically, of the 7,808 women with osteoporosis between the ages of 60 and 90 years enrolled in the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial, those who were assigned to receive twice yearly injections of 60 mg denosumab for 3 years were 68% less likely to develop a vertebral fracture and 40% less likely to develop a hip fracture than were women in the placebo group. Additionally, significantly increased bone mineral density was observed at all of the key sites measured.

By targeting the receptor activator of nuclear factor-kappaB ligand (RANKL), which is the primary mediator of osteoclast formation, denosumab blocks the production of the bone-destroying osteoclasts and by so doing improves the density, volume, and strength of both cortical and trabecular bone, according to the authors (N. Engl. J. Med. 2009;361:756–65).

Among the side effects reported in the FREEDOM and other clinical trials of denosumab, the most common include back pain, musculoskeletal pain, extremity pain, hypercholesterolemia, and urinary and bladder infections, according to a statement issued by the FDA. Serious adverse reactions include hypercalcemia, dermatologic conditions, and infections.

The significance of the long-term suppression of bone remodeling is unknown, according to a press release issued by Amgen.

“The long-term consequences of the degree of suppression of bone remodeling observed with [denosumab] may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing,” the release stated, warning that patients should be monitored for these adverse outcomes.

The FDA approval of denosumab includes a risk evaluation and mitigation strategy comprising a medication guide for patients and communications to health care providers explaining the risks and benefits of the drug.

The approval of denosumab was delayed in October 2009, when the FDA's Division of Reproductive and Urologic Products issued a Complete Response Letter for the biologics license application for denosumab in the treatment and prevention of postmenopausal osteoporosis, according to Amgen.

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peersupport intervention.

The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor.

After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups.

“The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000, so this was a fairly poor group,” Dr. Heisler said.

At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted.

“We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders,” she said.

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6.

“Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said.

In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager over the 6-month study period.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.”

Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, according to Dr. Heisler.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said.

“Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for intervention group as well,” she said.

There were no between-group differences in levels of diabetes-related emotional distress, she said.

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. “The actual number of calls could be higher, because some of the patients used their own phones for some or all of their calls,” Dr. Heisler explained.

Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

Although the study was limited by the inclusion of only male veterans and by its short time frame, “it's clear that the reciprocal care model can be an effective approach for helping diabetic patients help themselves,” Dr. Heisler said.

From an efficiency standpoint, “this model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” she said.

“Models like this increase the quality and intensity of assistance that we can provide to our diabetic patients and should be further refined and considered for clinical use,” Dr. Heisler said.

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peersupport intervention.

The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor.

After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups.

“The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000, so this was a fairly poor group,” Dr. Heisler said.

At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted.

“We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders,” she said.

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6.

“Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said.

In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager over the 6-month study period.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.”

Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, according to Dr. Heisler.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said.

“Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for intervention group as well,” she said.

There were no between-group differences in levels of diabetes-related emotional distress, she said.

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. “The actual number of calls could be higher, because some of the patients used their own phones for some or all of their calls,” Dr. Heisler explained.

Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

Although the study was limited by the inclusion of only male veterans and by its short time frame, “it's clear that the reciprocal care model can be an effective approach for helping diabetic patients help themselves,” Dr. Heisler said.

From an efficiency standpoint, “this model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” she said.

“Models like this increase the quality and intensity of assistance that we can provide to our diabetic patients and should be further refined and considered for clinical use,” Dr. Heisler said.

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peersupport intervention.

The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor.

After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups.

“The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000, so this was a fairly poor group,” Dr. Heisler said.

At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted.

“We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders,” she said.

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6.

“Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said.

In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager over the 6-month study period.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.”

Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, according to Dr. Heisler.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said.

“Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for intervention group as well,” she said.

There were no between-group differences in levels of diabetes-related emotional distress, she said.

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. “The actual number of calls could be higher, because some of the patients used their own phones for some or all of their calls,” Dr. Heisler explained.

Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

Although the study was limited by the inclusion of only male veterans and by its short time frame, “it's clear that the reciprocal care model can be an effective approach for helping diabetic patients help themselves,” Dr. Heisler said.

From an efficiency standpoint, “this model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” she said.

“Models like this increase the quality and intensity of assistance that we can provide to our diabetic patients and should be further refined and considered for clinical use,” Dr. Heisler said.

DESTIN, FLA. — Advances in biologic therapies have begun to change the treatment landscape for patients with systemic vasculitis, according to Dr. Philip Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“Biologics have led to the first new therapeutic option for patients with systemic vasculitis since cyclophosphamides became the standard of care in the 1970s,” Dr. Seo said at the meeting, which was sponsored by the Medical College of Virginia. “The most exciting thing to happen this past year has probably been the use of rituximab for Wegener's granulomatosis and microscopic polyangiitis.”

Preliminary results from the multicenter, randomized controlled RAVE (Rituximab for ANCA-Associated Vasculitis) trial, which were presented at the 2009 annual meeting of the American College of Rheumatology in Philadelphia, showed that the anti–B-cell agent rituximab was as effective as cyclophosphamide for these conditions, both of which are variants of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, Dr. Seo explained. Additionally, rituximab was superior to cyclophosphamide for patients who experienced severe disease flares, he said, noting that patients in the trial who were randomized to rituximab therapy experienced a near-complete depletion of B cells, which are ultimately the source of ANCA.

Rituximab may also be an important treatment option for patients with hepatitis C virus (HCV)–associated cryoglobulinemic vasculitis who do not respond to antiviral therapy, Dr. Seo said. About 5% of patients with HCV develop cryoglobulinemic vasculitis when their B lymphocytes produce abnormal proteins called cryoglobulins in response to the viral infection, he said. The resulting vasculitis may involve the skin, joints, kidneys, nerves, and other sites and can cause skin rashes, joint pain, weakness, fatigue, and numbness.

In an open-label, pilot study that was designed to assess the impact of combining rituximab with antiviral therapy, 16 patients with refractory HCV-related cryoglobulinemia were treated with weekly rituximab infusions for 4 weeks, combined with peginterferon plus ribavirin for 12 months (Ann. Rheum. Dis. 2008;67:1431-6). Of the 16 patients, 15 showed clinical improvement and 10 were complete responders, Dr. Seo said. “Nearly all of the patients had improvement in cutaneous ulcers, arthralgias, and purpura, and more than half had improvement in glomerulonephritis.”

In addition to anti–B-cell strategies, tumor necrosis factor blockade may have a therapeutic role in certain types of vasculitis as well, said Dr. Seo. For example, he said, in a recently reported case series of 25 patients with refractory Takayasu's arteritis, treatment with infliximab or etanercept for a median 28 months was associated with remission of the large-vessel vasculitis in a majority of the patients, which in turn resulted in the reduction or discontinuation of prednisone and other immunosuppressive drugs (Ann. Rheum. Dis. 2008;67:1567-9).

The role of biologic agents in the treatment of other forms of vasculitis is not yet clear, Dr. Seo said. For example, “although infliximab is effective for the treatment of Takayasu's, a trial [of the drug] in another large-vessel vasculitis, giant cell arteritis, was stopped due to lack of efficacy,” he said (Ann. Intern. Med. 2007;146:621-30). Also, a large study investigating the potential role of etanercept compared with cyclophosphamide and glucocorticoids in Wegener's granulomatosis showed no differences in the time to remission, frequency or duration of remission, frequency or severity of flares, or frequency or severity of adverse events (N. Engl. J. Med. 2005;352:351-61).

In all cases, “we have to proceed with caution, because the long-term consequences of [biologic] therapy are unknown, especially with rituximab and some of the newer agents coming down the pipe,” he warned.

“The TNF inhibitors may be associated with malignancy in some cases. Infliximab, in particular, is associated with a higher prevalence of malignancy in pediatric populations, and an increased risk of infection, including tuberculosis,” he said.

Regarding the anti–B-cell strategies, “the consequences of chronic B-cell depletion over years are largely unknown,” although studies have observed a decline in immunoglobulin levels in chronically treated patients, Dr. Seo said. Also, he noted, “rituximab may be associated with a relatively rare infection called progressive multifocal leukoencephalopathy.”

Biologics are clearly poised to become an important weapon in the fight against vasculitis, said Dr. Seo, “especially for patients in whom the cytotoxic drugs that we might normally use are contraindicated, such as older patients who might not be able to tolerate them, or patients who have already seen a cytotoxic agent maybe two or three times, who might not be able to tolerate it a fourth time.” Additionally, he said, “biologics may be well suited for younger patients, where you're concerned about fertility, because, unfortunately, about half of all patients on cytotoxic drugs will become infertile.”

Disclosures: Dr. Seo reported having no financial disclosures related to this presentation.

To watch a video interview of Dr. Seo, go to www.youtube.com/elsglobalmedicalnews

DESTIN, FLA. — Advances in biologic therapies have begun to change the treatment landscape for patients with systemic vasculitis, according to Dr. Philip Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“Biologics have led to the first new therapeutic option for patients with systemic vasculitis since cyclophosphamides became the standard of care in the 1970s,” Dr. Seo said at the meeting, which was sponsored by the Medical College of Virginia. “The most exciting thing to happen this past year has probably been the use of rituximab for Wegener's granulomatosis and microscopic polyangiitis.”

Preliminary results from the multicenter, randomized controlled RAVE (Rituximab for ANCA-Associated Vasculitis) trial, which were presented at the 2009 annual meeting of the American College of Rheumatology in Philadelphia, showed that the anti–B-cell agent rituximab was as effective as cyclophosphamide for these conditions, both of which are variants of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, Dr. Seo explained. Additionally, rituximab was superior to cyclophosphamide for patients who experienced severe disease flares, he said, noting that patients in the trial who were randomized to rituximab therapy experienced a near-complete depletion of B cells, which are ultimately the source of ANCA.

Rituximab may also be an important treatment option for patients with hepatitis C virus (HCV)–associated cryoglobulinemic vasculitis who do not respond to antiviral therapy, Dr. Seo said. About 5% of patients with HCV develop cryoglobulinemic vasculitis when their B lymphocytes produce abnormal proteins called cryoglobulins in response to the viral infection, he said. The resulting vasculitis may involve the skin, joints, kidneys, nerves, and other sites and can cause skin rashes, joint pain, weakness, fatigue, and numbness.

In an open-label, pilot study that was designed to assess the impact of combining rituximab with antiviral therapy, 16 patients with refractory HCV-related cryoglobulinemia were treated with weekly rituximab infusions for 4 weeks, combined with peginterferon plus ribavirin for 12 months (Ann. Rheum. Dis. 2008;67:1431-6). Of the 16 patients, 15 showed clinical improvement and 10 were complete responders, Dr. Seo said. “Nearly all of the patients had improvement in cutaneous ulcers, arthralgias, and purpura, and more than half had improvement in glomerulonephritis.”

In addition to anti–B-cell strategies, tumor necrosis factor blockade may have a therapeutic role in certain types of vasculitis as well, said Dr. Seo. For example, he said, in a recently reported case series of 25 patients with refractory Takayasu's arteritis, treatment with infliximab or etanercept for a median 28 months was associated with remission of the large-vessel vasculitis in a majority of the patients, which in turn resulted in the reduction or discontinuation of prednisone and other immunosuppressive drugs (Ann. Rheum. Dis. 2008;67:1567-9).

The role of biologic agents in the treatment of other forms of vasculitis is not yet clear, Dr. Seo said. For example, “although infliximab is effective for the treatment of Takayasu's, a trial [of the drug] in another large-vessel vasculitis, giant cell arteritis, was stopped due to lack of efficacy,” he said (Ann. Intern. Med. 2007;146:621-30). Also, a large study investigating the potential role of etanercept compared with cyclophosphamide and glucocorticoids in Wegener's granulomatosis showed no differences in the time to remission, frequency or duration of remission, frequency or severity of flares, or frequency or severity of adverse events (N. Engl. J. Med. 2005;352:351-61).

In all cases, “we have to proceed with caution, because the long-term consequences of [biologic] therapy are unknown, especially with rituximab and some of the newer agents coming down the pipe,” he warned.

“The TNF inhibitors may be associated with malignancy in some cases. Infliximab, in particular, is associated with a higher prevalence of malignancy in pediatric populations, and an increased risk of infection, including tuberculosis,” he said.

Regarding the anti–B-cell strategies, “the consequences of chronic B-cell depletion over years are largely unknown,” although studies have observed a decline in immunoglobulin levels in chronically treated patients, Dr. Seo said. Also, he noted, “rituximab may be associated with a relatively rare infection called progressive multifocal leukoencephalopathy.”

Biologics are clearly poised to become an important weapon in the fight against vasculitis, said Dr. Seo, “especially for patients in whom the cytotoxic drugs that we might normally use are contraindicated, such as older patients who might not be able to tolerate them, or patients who have already seen a cytotoxic agent maybe two or three times, who might not be able to tolerate it a fourth time.” Additionally, he said, “biologics may be well suited for younger patients, where you're concerned about fertility, because, unfortunately, about half of all patients on cytotoxic drugs will become infertile.”

Disclosures: Dr. Seo reported having no financial disclosures related to this presentation.

To watch a video interview of Dr. Seo, go to www.youtube.com/elsglobalmedicalnews

DESTIN, FLA. — Advances in biologic therapies have begun to change the treatment landscape for patients with systemic vasculitis, according to Dr. Philip Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“Biologics have led to the first new therapeutic option for patients with systemic vasculitis since cyclophosphamides became the standard of care in the 1970s,” Dr. Seo said at the meeting, which was sponsored by the Medical College of Virginia. “The most exciting thing to happen this past year has probably been the use of rituximab for Wegener's granulomatosis and microscopic polyangiitis.”

Preliminary results from the multicenter, randomized controlled RAVE (Rituximab for ANCA-Associated Vasculitis) trial, which were presented at the 2009 annual meeting of the American College of Rheumatology in Philadelphia, showed that the anti–B-cell agent rituximab was as effective as cyclophosphamide for these conditions, both of which are variants of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, Dr. Seo explained. Additionally, rituximab was superior to cyclophosphamide for patients who experienced severe disease flares, he said, noting that patients in the trial who were randomized to rituximab therapy experienced a near-complete depletion of B cells, which are ultimately the source of ANCA.

Rituximab may also be an important treatment option for patients with hepatitis C virus (HCV)–associated cryoglobulinemic vasculitis who do not respond to antiviral therapy, Dr. Seo said. About 5% of patients with HCV develop cryoglobulinemic vasculitis when their B lymphocytes produce abnormal proteins called cryoglobulins in response to the viral infection, he said. The resulting vasculitis may involve the skin, joints, kidneys, nerves, and other sites and can cause skin rashes, joint pain, weakness, fatigue, and numbness.

In an open-label, pilot study that was designed to assess the impact of combining rituximab with antiviral therapy, 16 patients with refractory HCV-related cryoglobulinemia were treated with weekly rituximab infusions for 4 weeks, combined with peginterferon plus ribavirin for 12 months (Ann. Rheum. Dis. 2008;67:1431-6). Of the 16 patients, 15 showed clinical improvement and 10 were complete responders, Dr. Seo said. “Nearly all of the patients had improvement in cutaneous ulcers, arthralgias, and purpura, and more than half had improvement in glomerulonephritis.”

In addition to anti–B-cell strategies, tumor necrosis factor blockade may have a therapeutic role in certain types of vasculitis as well, said Dr. Seo. For example, he said, in a recently reported case series of 25 patients with refractory Takayasu's arteritis, treatment with infliximab or etanercept for a median 28 months was associated with remission of the large-vessel vasculitis in a majority of the patients, which in turn resulted in the reduction or discontinuation of prednisone and other immunosuppressive drugs (Ann. Rheum. Dis. 2008;67:1567-9).

The role of biologic agents in the treatment of other forms of vasculitis is not yet clear, Dr. Seo said. For example, “although infliximab is effective for the treatment of Takayasu's, a trial [of the drug] in another large-vessel vasculitis, giant cell arteritis, was stopped due to lack of efficacy,” he said (Ann. Intern. Med. 2007;146:621-30). Also, a large study investigating the potential role of etanercept compared with cyclophosphamide and glucocorticoids in Wegener's granulomatosis showed no differences in the time to remission, frequency or duration of remission, frequency or severity of flares, or frequency or severity of adverse events (N. Engl. J. Med. 2005;352:351-61).

In all cases, “we have to proceed with caution, because the long-term consequences of [biologic] therapy are unknown, especially with rituximab and some of the newer agents coming down the pipe,” he warned.

“The TNF inhibitors may be associated with malignancy in some cases. Infliximab, in particular, is associated with a higher prevalence of malignancy in pediatric populations, and an increased risk of infection, including tuberculosis,” he said.

Regarding the anti–B-cell strategies, “the consequences of chronic B-cell depletion over years are largely unknown,” although studies have observed a decline in immunoglobulin levels in chronically treated patients, Dr. Seo said. Also, he noted, “rituximab may be associated with a relatively rare infection called progressive multifocal leukoencephalopathy.”

Biologics are clearly poised to become an important weapon in the fight against vasculitis, said Dr. Seo, “especially for patients in whom the cytotoxic drugs that we might normally use are contraindicated, such as older patients who might not be able to tolerate them, or patients who have already seen a cytotoxic agent maybe two or three times, who might not be able to tolerate it a fourth time.” Additionally, he said, “biologics may be well suited for younger patients, where you're concerned about fertility, because, unfortunately, about half of all patients on cytotoxic drugs will become infertile.”

Disclosures: Dr. Seo reported having no financial disclosures related to this presentation.

To watch a video interview of Dr. Seo, go to www.youtube.com/elsglobalmedicalnews

DESTIN, FLA. — The clinical spectrum of antiphospholipid syndrome has broadened substantially to include a range of clinical manifestations, including heart valve disease, livedo reticularis, thrombocytopenia, stroke, migraine, seizures, and cognitive dysfunction.

The potential cardiovascular and neurologic complications of antiphospholipid syndrome are especially concerning, said Dr. Graham Hughes, who along with his colleagues first described the prothrombotic condition in 1983.

“The clinical map is still being charted, and a number of recent clinical observations have added to our understanding of it,” said Dr. Hughes, professor of medicine at St. Thomas Hospital in London and director of the London Lupus Centre at London Bridge Hospital.

Antiphospholipid syndrome (APS), also called Hughes syndrome, is generally recognized as an autoimmune condition characterized by arterial and venous vascular thromboses and pregnancy complications in the presence of antiphospholipid (aPL) antibodies.

Dr. Hughes discussed several recent studies that argue for greater awareness, screening, and diagnosis of APS in primary care.

“We are seeing that APS is a major cause of heart attack, stroke, miscarriage, cognitive dysfunction, movement disorders, epilepsy and other conditions. There is a huge cost to delaying the diagnosis.”

If the syndrome is suspected, he said, “it's easy to diagnose and highly treatable,” primarily with aspirin, heparin, or warfarin.

A study of 344 acute coronary syndrome patients showed that 40% of the patients were aPL positive in one or more tests (Am. J. Clin. Pathol. 2009;132:613-20).

Additionally, in a report published in Lancet Neurology, the study population of women younger than 50 years of age who had experienced myocardial infarction or stroke had five times the risk of MI and a 40-fold increase in the risk of stroke, compared with matched healthy controls (Lancet Neurol. 2009;8:998-1005).

“The brain appears to be particularly susceptible to the syndrome,” Dr. Hughes stated, noting that, in addition to stroke—which is now “internationally recognized as an important manifestation” of APS—other neurologic presentations include migraine, memory loss, movement disorders, atypical multiple sclerosis, and epilepsy.

Importantly, new data suggest that a clinical link between migraine, stroke, and APS “is a very real possibility,” Dr. Hughes reported.

“Migraine and stroke are both prominent features of APS, and our own clinical experience with lupus patients at St. Thomas Hospital has been that many younger individuals with APS who have had a stroke—especially females—report a history of migraines prior to the stroke and a dramatic improvement in migraine during anticoagulation treatment,” he said. “Although the evidence is largely anecdotal, it may be that APS is a significant missing link between migraine and stroke.” In fact, he added, “it is now our practice in patients with [APS] and severe migraine attacks to use low-molecular-weight heparin to treat migraine and, potentially, avert stroke.”

In addition to rheumatologists, cardiologists, and neurologists, “more and more specialists are seeing patients with APS, including orthopedists and ear, nose, and throat surgeons,” Dr. Hughes noted, explaining that prospective cohort and case studies have demonstrated an association between aPL antibodies and avascular necrosis, often presenting as nontraumatic metatarsal, rib, and other fractures in individuals with no history of osteoporosis; in addition, middle-ear balance problems such as dizziness, acute vertigo, and tinnitus are all seen in APS.

A study of endothelial assessment in patients with APS suggests that preclinical atherosclerosis may be an important feature of APS.

Specifically, the results of high-resolution ultrasound studies showed significantly reduced endothelium-dependent, flow-mediated dilatation and increased carotid intima media thickness among 90 APS patients, compared with 90 age-, sex-, and cardiovascular risk factor–matched aPL-negative controls (Arthritis Rheum. 2006;54:557-8).

“We still don't know the exact mechanism for thrombosis. Studies have shown that aPL antibodies alter platelets, clotting proteins, and the blood vessel lining, but how each of these mechanisms contributes to APS is uncertain,” he said. “We also don't understand why patients get better when we anticoagulate.”

Disclosures: Dr. Hughes had no financial disclosures relative to his presentation.

DESTIN, FLA. — The clinical spectrum of antiphospholipid syndrome has broadened substantially to include a range of clinical manifestations, including heart valve disease, livedo reticularis, thrombocytopenia, stroke, migraine, seizures, and cognitive dysfunction.

The potential cardiovascular and neurologic complications of antiphospholipid syndrome are especially concerning, said Dr. Graham Hughes, who along with his colleagues first described the prothrombotic condition in 1983.

“The clinical map is still being charted, and a number of recent clinical observations have added to our understanding of it,” said Dr. Hughes, professor of medicine at St. Thomas Hospital in London and director of the London Lupus Centre at London Bridge Hospital.

Antiphospholipid syndrome (APS), also called Hughes syndrome, is generally recognized as an autoimmune condition characterized by arterial and venous vascular thromboses and pregnancy complications in the presence of antiphospholipid (aPL) antibodies.

Dr. Hughes discussed several recent studies that argue for greater awareness, screening, and diagnosis of APS in primary care.

“We are seeing that APS is a major cause of heart attack, stroke, miscarriage, cognitive dysfunction, movement disorders, epilepsy and other conditions. There is a huge cost to delaying the diagnosis.”

If the syndrome is suspected, he said, “it's easy to diagnose and highly treatable,” primarily with aspirin, heparin, or warfarin.

A study of 344 acute coronary syndrome patients showed that 40% of the patients were aPL positive in one or more tests (Am. J. Clin. Pathol. 2009;132:613-20).

Additionally, in a report published in Lancet Neurology, the study population of women younger than 50 years of age who had experienced myocardial infarction or stroke had five times the risk of MI and a 40-fold increase in the risk of stroke, compared with matched healthy controls (Lancet Neurol. 2009;8:998-1005).

“The brain appears to be particularly susceptible to the syndrome,” Dr. Hughes stated, noting that, in addition to stroke—which is now “internationally recognized as an important manifestation” of APS—other neurologic presentations include migraine, memory loss, movement disorders, atypical multiple sclerosis, and epilepsy.

Importantly, new data suggest that a clinical link between migraine, stroke, and APS “is a very real possibility,” Dr. Hughes reported.

“Migraine and stroke are both prominent features of APS, and our own clinical experience with lupus patients at St. Thomas Hospital has been that many younger individuals with APS who have had a stroke—especially females—report a history of migraines prior to the stroke and a dramatic improvement in migraine during anticoagulation treatment,” he said. “Although the evidence is largely anecdotal, it may be that APS is a significant missing link between migraine and stroke.” In fact, he added, “it is now our practice in patients with [APS] and severe migraine attacks to use low-molecular-weight heparin to treat migraine and, potentially, avert stroke.”

In addition to rheumatologists, cardiologists, and neurologists, “more and more specialists are seeing patients with APS, including orthopedists and ear, nose, and throat surgeons,” Dr. Hughes noted, explaining that prospective cohort and case studies have demonstrated an association between aPL antibodies and avascular necrosis, often presenting as nontraumatic metatarsal, rib, and other fractures in individuals with no history of osteoporosis; in addition, middle-ear balance problems such as dizziness, acute vertigo, and tinnitus are all seen in APS.

A study of endothelial assessment in patients with APS suggests that preclinical atherosclerosis may be an important feature of APS.

Specifically, the results of high-resolution ultrasound studies showed significantly reduced endothelium-dependent, flow-mediated dilatation and increased carotid intima media thickness among 90 APS patients, compared with 90 age-, sex-, and cardiovascular risk factor–matched aPL-negative controls (Arthritis Rheum. 2006;54:557-8).

“We still don't know the exact mechanism for thrombosis. Studies have shown that aPL antibodies alter platelets, clotting proteins, and the blood vessel lining, but how each of these mechanisms contributes to APS is uncertain,” he said. “We also don't understand why patients get better when we anticoagulate.”

Disclosures: Dr. Hughes had no financial disclosures relative to his presentation.

DESTIN, FLA. — The clinical spectrum of antiphospholipid syndrome has broadened substantially to include a range of clinical manifestations, including heart valve disease, livedo reticularis, thrombocytopenia, stroke, migraine, seizures, and cognitive dysfunction.

The potential cardiovascular and neurologic complications of antiphospholipid syndrome are especially concerning, said Dr. Graham Hughes, who along with his colleagues first described the prothrombotic condition in 1983.

“The clinical map is still being charted, and a number of recent clinical observations have added to our understanding of it,” said Dr. Hughes, professor of medicine at St. Thomas Hospital in London and director of the London Lupus Centre at London Bridge Hospital.

Antiphospholipid syndrome (APS), also called Hughes syndrome, is generally recognized as an autoimmune condition characterized by arterial and venous vascular thromboses and pregnancy complications in the presence of antiphospholipid (aPL) antibodies.

Dr. Hughes discussed several recent studies that argue for greater awareness, screening, and diagnosis of APS in primary care.

“We are seeing that APS is a major cause of heart attack, stroke, miscarriage, cognitive dysfunction, movement disorders, epilepsy and other conditions. There is a huge cost to delaying the diagnosis.”

If the syndrome is suspected, he said, “it's easy to diagnose and highly treatable,” primarily with aspirin, heparin, or warfarin.

A study of 344 acute coronary syndrome patients showed that 40% of the patients were aPL positive in one or more tests (Am. J. Clin. Pathol. 2009;132:613-20).

Additionally, in a report published in Lancet Neurology, the study population of women younger than 50 years of age who had experienced myocardial infarction or stroke had five times the risk of MI and a 40-fold increase in the risk of stroke, compared with matched healthy controls (Lancet Neurol. 2009;8:998-1005).

“The brain appears to be particularly susceptible to the syndrome,” Dr. Hughes stated, noting that, in addition to stroke—which is now “internationally recognized as an important manifestation” of APS—other neurologic presentations include migraine, memory loss, movement disorders, atypical multiple sclerosis, and epilepsy.

Importantly, new data suggest that a clinical link between migraine, stroke, and APS “is a very real possibility,” Dr. Hughes reported.

“Migraine and stroke are both prominent features of APS, and our own clinical experience with lupus patients at St. Thomas Hospital has been that many younger individuals with APS who have had a stroke—especially females—report a history of migraines prior to the stroke and a dramatic improvement in migraine during anticoagulation treatment,” he said. “Although the evidence is largely anecdotal, it may be that APS is a significant missing link between migraine and stroke.” In fact, he added, “it is now our practice in patients with [APS] and severe migraine attacks to use low-molecular-weight heparin to treat migraine and, potentially, avert stroke.”

In addition to rheumatologists, cardiologists, and neurologists, “more and more specialists are seeing patients with APS, including orthopedists and ear, nose, and throat surgeons,” Dr. Hughes noted, explaining that prospective cohort and case studies have demonstrated an association between aPL antibodies and avascular necrosis, often presenting as nontraumatic metatarsal, rib, and other fractures in individuals with no history of osteoporosis; in addition, middle-ear balance problems such as dizziness, acute vertigo, and tinnitus are all seen in APS.

A study of endothelial assessment in patients with APS suggests that preclinical atherosclerosis may be an important feature of APS.

Specifically, the results of high-resolution ultrasound studies showed significantly reduced endothelium-dependent, flow-mediated dilatation and increased carotid intima media thickness among 90 APS patients, compared with 90 age-, sex-, and cardiovascular risk factor–matched aPL-negative controls (Arthritis Rheum. 2006;54:557-8).

“We still don't know the exact mechanism for thrombosis. Studies have shown that aPL antibodies alter platelets, clotting proteins, and the blood vessel lining, but how each of these mechanisms contributes to APS is uncertain,” he said. “We also don't understand why patients get better when we anticoagulate.”

Disclosures: Dr. Hughes had no financial disclosures relative to his presentation.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. Office-based buprenorphine/naloxone treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74).

The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

About “25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. Office-based buprenorphine/naloxone treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74).

The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

About “25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. Office-based buprenorphine/naloxone treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74).

The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

About “25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

MINNEAPOLIS – Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. The office-based treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365–74). The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while they are incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Limitations of the study include reliance on self-reported data for assessing incarceration and delinquency, said Dr. Fiellin, though he noted that all of the measures were obtained from previously validated instruments.

In addition, “the initial randomized trial was not designed to detect differences based on history of incarceration,” he said.

MINNEAPOLIS – Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. The office-based treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365–74). The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while they are incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Limitations of the study include reliance on self-reported data for assessing incarceration and delinquency, said Dr. Fiellin, though he noted that all of the measures were obtained from previously validated instruments.

In addition, “the initial randomized trial was not designed to detect differences based on history of incarceration,” he said.

MINNEAPOLIS – Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported. The office-based treatment also can be an avenue for addressing other negative health consequences of chronic addiction, including referral for hepatitis C treatment, when indicated, as well as vocational and mental health programs.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing in conjunction with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365–74). The investigators compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone (Suboxone) was 17.9 mg and 18.0 mg for the previously incarcerated and never incarcerated patients, respectively, he said.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin said. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment. “Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while they are incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Limitations of the study include reliance on self-reported data for assessing incarceration and delinquency, said Dr. Fiellin, though he noted that all of the measures were obtained from previously validated instruments.

In addition, “the initial randomized trial was not designed to detect differences based on history of incarceration,” he said.

Major Finding: Central line–associated bloodstream infections were reduced by 18% nationwide in 2009.

Data Source: CDC health care–associated infection summary data report of national and state specific infections.

Disclosures: None was reported.

The overall number of central line–associated bloodstream infections during the first half of 2009 in states with legislative mandates to report such infections was 18% lower than predicted based on national estimates from the previous 3 years.

That finding emerged from a health care–associated infections (HAIs) summary report issued by the Centers for Disease Control and Prevention that includes overall national data on central line–associated bloodstream infections (CLABSIs) and, for the first time, state-specific data from health care facilities in states that mandate CLABSI reporting to the CDC's National Healthcare Safety Network, according to Dr. Don Wright, deputy assistant secretary for healthcare quality in the Department of Health and Human Services' Office of Public Health and Science.

The report also compares national and state data from January to June 2009 with national data from 2006 to 2008 using standardized infection ratio (SIR) calculations.

The report is a “benchmark for progress” on the national goals of the HHS Action Plan to Prevent Healthcare-Associated Infections (www.hhs.gov/ophs/initiatives/hai

According to the report, in the 17 states that, as of June 30, 2009, had mandated the reporting of CLABSIs to their state health departments, 1,538 health care facilities reported 4,615 CLABSIs from January to June 2009—nearly 1,000 fewer than the 5,619 that were predicted.

Eleven of the 17 states had an SIR significantly less than the nominal value 1.0 (representing the number of expected infections), while only 2 had SIRs that were significantly higher than 1.0, said Dr. Arjun Srinivasan, associate director for the CDC's Healthcare-Associated Infection Prevention Program. In nearly all of the states with mandated reporting, at least 25% of health care facilities reported no CLABSIs, the report noted.

Although the initial results are encouraging and represent early progress in the comprehensive strategy to reduce, prevent, and ultimately eliminate HAIs outlined in the HHS Action Plan, the current report “is only the first step,” Dr. Srinivasan said, noting that the “real tests” will be every 6 months, with the release of updated reports that allow comparisons of state-specific progress over time.

Although the summary report uses an SIR of 1.0 to indicate the predicted number of CLABSIs, “1.0 is not our ultimate goal. The ratio can be reduced much further,” Dr. Srinivasan said, noting that most CLABSIs are preventable. The 18% national reduction observed thus far reflects a broader implementation of infection control guidelines, enhanced tracking and measurement, and the combined efforts of clinicians, state health departments, federal agencies, professional organizations, and consumer advocates to enhance prevention efforts, “but more still has to be done” to meet the goal of a 50% reduction by 2013 outlined in the action plan, he said.

The Association for Professionals in Infection Control and Epidemiology (APIC) said in a statement that it was encouraged by the report's findings. “Many of our member facilities have seen that central line–associated bloodstream infections can be reduced to zero, and that in many instances 'zero' can be maintained,” the APIC said.

The CDC report is found at www.cdc.gov/hai/statesummary.html

Major Finding: Central line–associated bloodstream infections were reduced by 18% nationwide in 2009.

Data Source: CDC health care–associated infection summary data report of national and state specific infections.

Disclosures: None was reported.

The overall number of central line–associated bloodstream infections during the first half of 2009 in states with legislative mandates to report such infections was 18% lower than predicted based on national estimates from the previous 3 years.

That finding emerged from a health care–associated infections (HAIs) summary report issued by the Centers for Disease Control and Prevention that includes overall national data on central line–associated bloodstream infections (CLABSIs) and, for the first time, state-specific data from health care facilities in states that mandate CLABSI reporting to the CDC's National Healthcare Safety Network, according to Dr. Don Wright, deputy assistant secretary for healthcare quality in the Department of Health and Human Services' Office of Public Health and Science.

The report also compares national and state data from January to June 2009 with national data from 2006 to 2008 using standardized infection ratio (SIR) calculations.

The report is a “benchmark for progress” on the national goals of the HHS Action Plan to Prevent Healthcare-Associated Infections (www.hhs.gov/ophs/initiatives/hai

According to the report, in the 17 states that, as of June 30, 2009, had mandated the reporting of CLABSIs to their state health departments, 1,538 health care facilities reported 4,615 CLABSIs from January to June 2009—nearly 1,000 fewer than the 5,619 that were predicted.

Eleven of the 17 states had an SIR significantly less than the nominal value 1.0 (representing the number of expected infections), while only 2 had SIRs that were significantly higher than 1.0, said Dr. Arjun Srinivasan, associate director for the CDC's Healthcare-Associated Infection Prevention Program. In nearly all of the states with mandated reporting, at least 25% of health care facilities reported no CLABSIs, the report noted.

Although the initial results are encouraging and represent early progress in the comprehensive strategy to reduce, prevent, and ultimately eliminate HAIs outlined in the HHS Action Plan, the current report “is only the first step,” Dr. Srinivasan said, noting that the “real tests” will be every 6 months, with the release of updated reports that allow comparisons of state-specific progress over time.

Although the summary report uses an SIR of 1.0 to indicate the predicted number of CLABSIs, “1.0 is not our ultimate goal. The ratio can be reduced much further,” Dr. Srinivasan said, noting that most CLABSIs are preventable. The 18% national reduction observed thus far reflects a broader implementation of infection control guidelines, enhanced tracking and measurement, and the combined efforts of clinicians, state health departments, federal agencies, professional organizations, and consumer advocates to enhance prevention efforts, “but more still has to be done” to meet the goal of a 50% reduction by 2013 outlined in the action plan, he said.

The Association for Professionals in Infection Control and Epidemiology (APIC) said in a statement that it was encouraged by the report's findings. “Many of our member facilities have seen that central line–associated bloodstream infections can be reduced to zero, and that in many instances 'zero' can be maintained,” the APIC said.

The CDC report is found at www.cdc.gov/hai/statesummary.html

Major Finding: Central line–associated bloodstream infections were reduced by 18% nationwide in 2009.

Data Source: CDC health care–associated infection summary data report of national and state specific infections.

Disclosures: None was reported.

The overall number of central line–associated bloodstream infections during the first half of 2009 in states with legislative mandates to report such infections was 18% lower than predicted based on national estimates from the previous 3 years.

That finding emerged from a health care–associated infections (HAIs) summary report issued by the Centers for Disease Control and Prevention that includes overall national data on central line–associated bloodstream infections (CLABSIs) and, for the first time, state-specific data from health care facilities in states that mandate CLABSI reporting to the CDC's National Healthcare Safety Network, according to Dr. Don Wright, deputy assistant secretary for healthcare quality in the Department of Health and Human Services' Office of Public Health and Science.

The report also compares national and state data from January to June 2009 with national data from 2006 to 2008 using standardized infection ratio (SIR) calculations.

The report is a “benchmark for progress” on the national goals of the HHS Action Plan to Prevent Healthcare-Associated Infections (www.hhs.gov/ophs/initiatives/hai

According to the report, in the 17 states that, as of June 30, 2009, had mandated the reporting of CLABSIs to their state health departments, 1,538 health care facilities reported 4,615 CLABSIs from January to June 2009—nearly 1,000 fewer than the 5,619 that were predicted.

Eleven of the 17 states had an SIR significantly less than the nominal value 1.0 (representing the number of expected infections), while only 2 had SIRs that were significantly higher than 1.0, said Dr. Arjun Srinivasan, associate director for the CDC's Healthcare-Associated Infection Prevention Program. In nearly all of the states with mandated reporting, at least 25% of health care facilities reported no CLABSIs, the report noted.

Although the initial results are encouraging and represent early progress in the comprehensive strategy to reduce, prevent, and ultimately eliminate HAIs outlined in the HHS Action Plan, the current report “is only the first step,” Dr. Srinivasan said, noting that the “real tests” will be every 6 months, with the release of updated reports that allow comparisons of state-specific progress over time.

Although the summary report uses an SIR of 1.0 to indicate the predicted number of CLABSIs, “1.0 is not our ultimate goal. The ratio can be reduced much further,” Dr. Srinivasan said, noting that most CLABSIs are preventable. The 18% national reduction observed thus far reflects a broader implementation of infection control guidelines, enhanced tracking and measurement, and the combined efforts of clinicians, state health departments, federal agencies, professional organizations, and consumer advocates to enhance prevention efforts, “but more still has to be done” to meet the goal of a 50% reduction by 2013 outlined in the action plan, he said.

The Association for Professionals in Infection Control and Epidemiology (APIC) said in a statement that it was encouraged by the report's findings. “Many of our member facilities have seen that central line–associated bloodstream infections can be reduced to zero, and that in many instances 'zero' can be maintained,” the APIC said.

The CDC report is found at www.cdc.gov/hai/statesummary.html