Mary Ann Moon

Patients with bullous pemphigoid have a high prevalence of neurologic disorders, particularly cerebrovascular disease and dementia, according to a report in the November issue of the Archives of Dermatology.

Given the timing of the onset of the two disorders, "it is tempting to speculate that certain neurologic conditions can predispose to BP [bullous pemphigoid]," noted Dr. Kathy Taghipour of the department of dermatology at Oxford (England) Radcliffe Hospitals and her associates.

Bullous pemphigoid is a debilitating autoimmune skin disease characterized by large, tense blisters, which typically affect the elderly. In case reports, various neurologic disorders have been described in association with the disease, including stroke, dementia, multiple sclerosis, epilepsy, Parkinson’s disease, Shy-Drager syndrome (Multiple system atrophy), and amyotrophic lateral sclerosis. However, "robust epidemiological evidence for the association is lacking," Dr. Taghipour and her colleagues reported.

Therefore, the investigators performed what they described as the first case-control study to examine a possible link, enrolling 90 consecutive patients diagnosed with BP at a single specialist outpatient center for immunobullous diseases between 2004 and 2008. A total of 141 age- and sex-matched patients attending a nearby skin tumor clinic served as a control group. None of the control patients had inflammatory skin disease.

The medical records of all the study patients were reviewed for the presence of neurologic disease.

A total of 42 BP patients (46.7%) had at least one neurologic disorder confirmed by a hospital physician, psychiatrist, or neurologist. In contrast, only 16 of the control subjects (11.3%) had neurologic disorders. Six patients with BP had more than one neurologic disorder.

Two particular neurologic disorders – cerebrovascular disease and dementia – accounted for almost all of the difference. Compared with control subjects, patients with BP were at significantly increased odds of having cerebrovascular disease or dementia, with adjusted odds ratios of 6.0 and 7.9, respectively.

It was possible to determine the date of onset of the neurologic disorders in 36 of the patients with BP (85.7%); in 26 (72.2%), the neurologic disorder preceded BP. In another five patients, both disorders were diagnosed within the same year. The neurologic disorder was diagnosed after BP in five cases, Dr. Taghipour and her associates reported (Arch. Dermatol. 2010;146:1251-4).

The median interval between diagnosis of the neurologic disease and diagnosis of BP was 5.5 years.

Although the underlying mechanism for this association is not yet known, it "could potentially be explained by the presence of an immunologic cross-reactivity between the skin and the brain," the investigators reported.

"It is plausible to postulate that neurologic disorders may expose [certain neuronal] antigens to the immune system and trigger a subsequent immune response. Many neurologic conditions, in particular cerebrovascular diseases, lead to damage in the blood-brain barrier, which may in turn facilitate autoimmunity toward neuronal antigens and cross-reaction with skin," they wrote.

Patients with bullous pemphigoid have a high prevalence of neurologic disorders, particularly cerebrovascular disease and dementia, according to a report in the November issue of the Archives of Dermatology.

Given the timing of the onset of the two disorders, "it is tempting to speculate that certain neurologic conditions can predispose to BP [bullous pemphigoid]," noted Dr. Kathy Taghipour of the department of dermatology at Oxford (England) Radcliffe Hospitals and her associates.

Bullous pemphigoid is a debilitating autoimmune skin disease characterized by large, tense blisters, which typically affect the elderly. In case reports, various neurologic disorders have been described in association with the disease, including stroke, dementia, multiple sclerosis, epilepsy, Parkinson’s disease, Shy-Drager syndrome (Multiple system atrophy), and amyotrophic lateral sclerosis. However, "robust epidemiological evidence for the association is lacking," Dr. Taghipour and her colleagues reported.

Therefore, the investigators performed what they described as the first case-control study to examine a possible link, enrolling 90 consecutive patients diagnosed with BP at a single specialist outpatient center for immunobullous diseases between 2004 and 2008. A total of 141 age- and sex-matched patients attending a nearby skin tumor clinic served as a control group. None of the control patients had inflammatory skin disease.

The medical records of all the study patients were reviewed for the presence of neurologic disease.

A total of 42 BP patients (46.7%) had at least one neurologic disorder confirmed by a hospital physician, psychiatrist, or neurologist. In contrast, only 16 of the control subjects (11.3%) had neurologic disorders. Six patients with BP had more than one neurologic disorder.

Two particular neurologic disorders – cerebrovascular disease and dementia – accounted for almost all of the difference. Compared with control subjects, patients with BP were at significantly increased odds of having cerebrovascular disease or dementia, with adjusted odds ratios of 6.0 and 7.9, respectively.

It was possible to determine the date of onset of the neurologic disorders in 36 of the patients with BP (85.7%); in 26 (72.2%), the neurologic disorder preceded BP. In another five patients, both disorders were diagnosed within the same year. The neurologic disorder was diagnosed after BP in five cases, Dr. Taghipour and her associates reported (Arch. Dermatol. 2010;146:1251-4).

The median interval between diagnosis of the neurologic disease and diagnosis of BP was 5.5 years.

Although the underlying mechanism for this association is not yet known, it "could potentially be explained by the presence of an immunologic cross-reactivity between the skin and the brain," the investigators reported.

"It is plausible to postulate that neurologic disorders may expose [certain neuronal] antigens to the immune system and trigger a subsequent immune response. Many neurologic conditions, in particular cerebrovascular diseases, lead to damage in the blood-brain barrier, which may in turn facilitate autoimmunity toward neuronal antigens and cross-reaction with skin," they wrote.

Patients with bullous pemphigoid have a high prevalence of neurologic disorders, particularly cerebrovascular disease and dementia, according to a report in the November issue of the Archives of Dermatology.

Given the timing of the onset of the two disorders, "it is tempting to speculate that certain neurologic conditions can predispose to BP [bullous pemphigoid]," noted Dr. Kathy Taghipour of the department of dermatology at Oxford (England) Radcliffe Hospitals and her associates.

Bullous pemphigoid is a debilitating autoimmune skin disease characterized by large, tense blisters, which typically affect the elderly. In case reports, various neurologic disorders have been described in association with the disease, including stroke, dementia, multiple sclerosis, epilepsy, Parkinson’s disease, Shy-Drager syndrome (Multiple system atrophy), and amyotrophic lateral sclerosis. However, "robust epidemiological evidence for the association is lacking," Dr. Taghipour and her colleagues reported.

Therefore, the investigators performed what they described as the first case-control study to examine a possible link, enrolling 90 consecutive patients diagnosed with BP at a single specialist outpatient center for immunobullous diseases between 2004 and 2008. A total of 141 age- and sex-matched patients attending a nearby skin tumor clinic served as a control group. None of the control patients had inflammatory skin disease.

The medical records of all the study patients were reviewed for the presence of neurologic disease.

A total of 42 BP patients (46.7%) had at least one neurologic disorder confirmed by a hospital physician, psychiatrist, or neurologist. In contrast, only 16 of the control subjects (11.3%) had neurologic disorders. Six patients with BP had more than one neurologic disorder.

Two particular neurologic disorders – cerebrovascular disease and dementia – accounted for almost all of the difference. Compared with control subjects, patients with BP were at significantly increased odds of having cerebrovascular disease or dementia, with adjusted odds ratios of 6.0 and 7.9, respectively.

It was possible to determine the date of onset of the neurologic disorders in 36 of the patients with BP (85.7%); in 26 (72.2%), the neurologic disorder preceded BP. In another five patients, both disorders were diagnosed within the same year. The neurologic disorder was diagnosed after BP in five cases, Dr. Taghipour and her associates reported (Arch. Dermatol. 2010;146:1251-4).

The median interval between diagnosis of the neurologic disease and diagnosis of BP was 5.5 years.

Although the underlying mechanism for this association is not yet known, it "could potentially be explained by the presence of an immunologic cross-reactivity between the skin and the brain," the investigators reported.

"It is plausible to postulate that neurologic disorders may expose [certain neuronal] antigens to the immune system and trigger a subsequent immune response. Many neurologic conditions, in particular cerebrovascular diseases, lead to damage in the blood-brain barrier, which may in turn facilitate autoimmunity toward neuronal antigens and cross-reaction with skin," they wrote.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online Nov. 16 in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography’s sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was "strikingly" higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography’s sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings "support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition," they noted, with the caveat that cost effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors "behaved completely differently" from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online Nov. 16 in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography’s sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was "strikingly" higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography’s sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings "support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition," they noted, with the caveat that cost effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors "behaved completely differently" from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online Nov. 16 in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography’s sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was "strikingly" higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography’s sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings "support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition," they noted, with the caveat that cost effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors "behaved completely differently" from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

Major Finding: Among patients addicted to opioids, 40% were able to discontinue illicit drug use for 4 months and 37% for 6 months after receiving buprenorphine implants, while only 28% and 22%, respectively, discontinued illicit drug use after receiving placebo implants.

Data Source: A phase III, randomized placebo-controlled trial of 163 patients treated at 18 U.S. clinical centers and followed for 6 months.

Disclosures: This study was funded by Titan Pharmaceuticals, maker of the buprenorphine implants, which was involved in the design and management of the study, data collection and analysis, and preparation and approval of the manuscript. Dr. Ling and his associates reported numerous ties to drug and device manufacturers.

Buprenorphine implants helped approximately 40% of patients addicted to opioids markedly reduce their drug use for 6 months in a phase III study of this new method of delivery.

In addition, two-thirds of the study subjects who received the implants completed 24 weeks of treatment without experiencing cravings or withdrawal symptoms compelling them to drop out, said Dr. Walter Ling of the UCLA Integrated Substance Abuse Programs, Los Angeles, and his associates.

In comparison, studies of sublingual buprenorphine found a median adherence of only 40 days in clinical settings, and 6-month clinical trials report subject retention rates of 35%-38%, the investigators noted.

The implantable formulation of buprenorphine was developed to address dependent patients' problems with adherence and “diversion,” or using the drug for some purpose other than treatment, such as selling it. The implants deliver an initial pulse of buprenorphine followed by the release of a constant, low level for 6 months.

Dr. Ling and his colleagues performed their industry-sponsored phase III study at 18 community addiction treatment centers across the United States. In all, 108 subjects were randomly assigned to receive four buprenorphine implants and 55 to receive four placebo implants in the subdermal space in the inner side of the nondominant arm.

The study subjects were allowed to receive supplemental sublingual buprenorphine-plus-naloxone tablets if they experienced significant withdrawal symptoms or cravings. They also were allowed to get one additional implant if necessary. All also received individual drug counseling twice a week for 3 months and weekly thereafter.

The patients' use of illicit drugs was monitored throughout the study by urinalyses done 3 times per week.

The primary outcome was early treatment response, assessed as the percentage of the 48 urine samples obtained during the first 16 weeks of the trial that were negative for illicit opioids. This rate was 40% with the buprenorphine implants, vs. 28% with the placebo implants, the researchers said (JAMA 2010;304:1576-83).

For the full 6-month treatment period, in which 72 urine samples were analyzed for each subject, 37% were negative for illicit opioids in the buprenorphine group, compared with 22% for placebo.

Treatment adherence was significantly better with the active treatment at 16 weeks (82% with buprenorphine vs. 51% with placebo) and at the conclusion of the study (66% vs. 31%). Throughout the study, the implant group also had significantly lower scores on measures of opiate withdrawal and opioid craving. No patients who received buprenorphine implants were classified as treatment failures, while 31% who received placebo implants were.

Major Finding: Among patients addicted to opioids, 40% were able to discontinue illicit drug use for 4 months and 37% for 6 months after receiving buprenorphine implants, while only 28% and 22%, respectively, discontinued illicit drug use after receiving placebo implants.

Data Source: A phase III, randomized placebo-controlled trial of 163 patients treated at 18 U.S. clinical centers and followed for 6 months.

Disclosures: This study was funded by Titan Pharmaceuticals, maker of the buprenorphine implants, which was involved in the design and management of the study, data collection and analysis, and preparation and approval of the manuscript. Dr. Ling and his associates reported numerous ties to drug and device manufacturers.

Buprenorphine implants helped approximately 40% of patients addicted to opioids markedly reduce their drug use for 6 months in a phase III study of this new method of delivery.

In addition, two-thirds of the study subjects who received the implants completed 24 weeks of treatment without experiencing cravings or withdrawal symptoms compelling them to drop out, said Dr. Walter Ling of the UCLA Integrated Substance Abuse Programs, Los Angeles, and his associates.

In comparison, studies of sublingual buprenorphine found a median adherence of only 40 days in clinical settings, and 6-month clinical trials report subject retention rates of 35%-38%, the investigators noted.

The implantable formulation of buprenorphine was developed to address dependent patients' problems with adherence and “diversion,” or using the drug for some purpose other than treatment, such as selling it. The implants deliver an initial pulse of buprenorphine followed by the release of a constant, low level for 6 months.

Dr. Ling and his colleagues performed their industry-sponsored phase III study at 18 community addiction treatment centers across the United States. In all, 108 subjects were randomly assigned to receive four buprenorphine implants and 55 to receive four placebo implants in the subdermal space in the inner side of the nondominant arm.

The study subjects were allowed to receive supplemental sublingual buprenorphine-plus-naloxone tablets if they experienced significant withdrawal symptoms or cravings. They also were allowed to get one additional implant if necessary. All also received individual drug counseling twice a week for 3 months and weekly thereafter.

The patients' use of illicit drugs was monitored throughout the study by urinalyses done 3 times per week.

The primary outcome was early treatment response, assessed as the percentage of the 48 urine samples obtained during the first 16 weeks of the trial that were negative for illicit opioids. This rate was 40% with the buprenorphine implants, vs. 28% with the placebo implants, the researchers said (JAMA 2010;304:1576-83).

For the full 6-month treatment period, in which 72 urine samples were analyzed for each subject, 37% were negative for illicit opioids in the buprenorphine group, compared with 22% for placebo.

Treatment adherence was significantly better with the active treatment at 16 weeks (82% with buprenorphine vs. 51% with placebo) and at the conclusion of the study (66% vs. 31%). Throughout the study, the implant group also had significantly lower scores on measures of opiate withdrawal and opioid craving. No patients who received buprenorphine implants were classified as treatment failures, while 31% who received placebo implants were.

Major Finding: Among patients addicted to opioids, 40% were able to discontinue illicit drug use for 4 months and 37% for 6 months after receiving buprenorphine implants, while only 28% and 22%, respectively, discontinued illicit drug use after receiving placebo implants.

Data Source: A phase III, randomized placebo-controlled trial of 163 patients treated at 18 U.S. clinical centers and followed for 6 months.

Disclosures: This study was funded by Titan Pharmaceuticals, maker of the buprenorphine implants, which was involved in the design and management of the study, data collection and analysis, and preparation and approval of the manuscript. Dr. Ling and his associates reported numerous ties to drug and device manufacturers.

Buprenorphine implants helped approximately 40% of patients addicted to opioids markedly reduce their drug use for 6 months in a phase III study of this new method of delivery.

In addition, two-thirds of the study subjects who received the implants completed 24 weeks of treatment without experiencing cravings or withdrawal symptoms compelling them to drop out, said Dr. Walter Ling of the UCLA Integrated Substance Abuse Programs, Los Angeles, and his associates.

In comparison, studies of sublingual buprenorphine found a median adherence of only 40 days in clinical settings, and 6-month clinical trials report subject retention rates of 35%-38%, the investigators noted.

The implantable formulation of buprenorphine was developed to address dependent patients' problems with adherence and “diversion,” or using the drug for some purpose other than treatment, such as selling it. The implants deliver an initial pulse of buprenorphine followed by the release of a constant, low level for 6 months.

Dr. Ling and his colleagues performed their industry-sponsored phase III study at 18 community addiction treatment centers across the United States. In all, 108 subjects were randomly assigned to receive four buprenorphine implants and 55 to receive four placebo implants in the subdermal space in the inner side of the nondominant arm.

The study subjects were allowed to receive supplemental sublingual buprenorphine-plus-naloxone tablets if they experienced significant withdrawal symptoms or cravings. They also were allowed to get one additional implant if necessary. All also received individual drug counseling twice a week for 3 months and weekly thereafter.

The patients' use of illicit drugs was monitored throughout the study by urinalyses done 3 times per week.

The primary outcome was early treatment response, assessed as the percentage of the 48 urine samples obtained during the first 16 weeks of the trial that were negative for illicit opioids. This rate was 40% with the buprenorphine implants, vs. 28% with the placebo implants, the researchers said (JAMA 2010;304:1576-83).

For the full 6-month treatment period, in which 72 urine samples were analyzed for each subject, 37% were negative for illicit opioids in the buprenorphine group, compared with 22% for placebo.

Treatment adherence was significantly better with the active treatment at 16 weeks (82% with buprenorphine vs. 51% with placebo) and at the conclusion of the study (66% vs. 31%). Throughout the study, the implant group also had significantly lower scores on measures of opiate withdrawal and opioid craving. No patients who received buprenorphine implants were classified as treatment failures, while 31% who received placebo implants were.

Major Finding: The rate of blood pressure control was a significant 8% higher in black men attending barbershops that participated in an active intervention than in those attending a comparison group of barbershops in Texas.

Data Source: BARBER-1, a cluster-randomized controlled trial assessing a barbershop-based health promotion program aimed at identifying hypertension in black men and referring them to a physician for treatment.

Disclosures: The National Heart, Lung, and Blood Institute, the Donald W. Reynolds Foundation, the Aetna Foundation Regional Health Disparity Program, Pfizer, Biovail, Cedars-Sinai Heart Institute, the Lincy Foundation, and the Robert Wood Johnson Foundation supported the trial. Dr. Victor reported ties to Pfizer and Biovail.

An outreach program in which barbers served as health educators – monitoring their black male clients' hypertension and referring them for medical treatment when necessary – improved the rate of blood pressure control by about 9% over 10 months, according to a report published online in the Archives of Internal Medicine

The intervention, which was tested in 17 black-owned barbershops in a single Texas county, motivated about half the hypertensive patrons at participating barbershops to see a physician, and reduced their systolic blood pressure by a mean of 2.5 mm Hg, said Dr. Ronald G. Victor of the University of Texas Southwest Medical Center, Dallas, and his associates.

“If the intervention could be implemented in the approximately 18,000 black-owned barbershops in the United States to reduce blood pressure by 2.5 mm Hg in the approximately 50% of hypertensive U.S. black men who patronize these barbershops (2.2 million persons), we project that about 800 fewer myocardial infarctions, 550 fewer strokes, and 900 fewer deaths would occur in the first year alone,” the investigators noted.

Black-owned barbershops “are rapidly gaining traction as potential community partners for health promotion programs targeting hypertension as well as diabetes, prostate cancer, and other diseases that disproportionately affect black men,” the researchers said.

Such barbershops “are a cultural institution that draws a large and loyal male clientele and provides an open forum for discussion of numerous topics, including health, with influential peers.”

Dr. Victor and his colleagues conducted their study by offering free blood pressure screening to patrons of 17 barbershops representing four geographic sectors with sizeable black populations in the Barber-Assisted Reduction in Blood Pressure in Ethnic Residents (BARBER-1). Nine barbershops with 695 patrons who were found to have hypertension then were randomly allocated to the intervention, and eight barbershops with 602 patrons who had hypertension were randomly allocated to a comparison group.

Most of the barbershop clients were middle income.

The comparison group was not strictly a control group; patrons there underwent two BP screenings at baseline and received standard written explanations and recommendations for physician follow-up, because failing to advise them would have been unethical. The comparison barbershops also made available American Heart Association pamphlets entitled “High Blood Pressure in African Americans.”

For the intervention, barbers continually offered all male clients blood pressure checks along with their haircuts. They displayed large posters depicting authentic stories of other male hypertensive patrons of the same shop modeling treatment-seeking behavior, using the model's own words to tell the story. Barbers and other male patrons also discussed the issue conversationally.

The barbers were trained, equipped, and paid to conduct BP testing and interpret the results, with the main focus on encouraging clients who had positive results to consult a physician. They referred clients who had no physician to a nursing staff that then referred them to local physicians or safety-net clinics. Barbers also gave patrons found to be hypertensive a wallet-sized card for the physician to sign, documenting an office visit concerning hypertension.

The barbers were paid $3 for every recorded blood pressure they took, $10 for every referral they made to the nursing staff, and $50 for every BP card that clients returned to them with physicians' signatures. Patrons received free haircuts (a $12 value) for every BP card they returned with a physician's signature.

Overall, nearly half of the patrons who were screened had high blood pressure; 78% of them were already aware that they were hypertensive, and 69% said they were taking treatment for HT, yet only 38% had their blood pressure under control.

Barbers were able to measure blood pressure in three of every four patrons who had hypertension, and each hypertensive client averaged eight blood pressure checks during the 10-month study. “The barbers motivated 50% of their patrons with elevated BP readings to visit a physician,” the researchers said.

The rate of blood pressure control – the number of men who achieved blood pressure control during BARBER-1 – improved by about 10% in the comparison group, but improved by an additional and significant 8% in the intervention group. The intervention group also showed an absolute decrease of 2.5 mm Hg in systolic blood pressure compared with the control group, a secondary outcome of borderline significance, the investigators said (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.390]).

Major Finding: The rate of blood pressure control was a significant 8% higher in black men attending barbershops that participated in an active intervention than in those attending a comparison group of barbershops in Texas.

Data Source: BARBER-1, a cluster-randomized controlled trial assessing a barbershop-based health promotion program aimed at identifying hypertension in black men and referring them to a physician for treatment.

Disclosures: The National Heart, Lung, and Blood Institute, the Donald W. Reynolds Foundation, the Aetna Foundation Regional Health Disparity Program, Pfizer, Biovail, Cedars-Sinai Heart Institute, the Lincy Foundation, and the Robert Wood Johnson Foundation supported the trial. Dr. Victor reported ties to Pfizer and Biovail.

An outreach program in which barbers served as health educators – monitoring their black male clients' hypertension and referring them for medical treatment when necessary – improved the rate of blood pressure control by about 9% over 10 months, according to a report published online in the Archives of Internal Medicine

The intervention, which was tested in 17 black-owned barbershops in a single Texas county, motivated about half the hypertensive patrons at participating barbershops to see a physician, and reduced their systolic blood pressure by a mean of 2.5 mm Hg, said Dr. Ronald G. Victor of the University of Texas Southwest Medical Center, Dallas, and his associates.

“If the intervention could be implemented in the approximately 18,000 black-owned barbershops in the United States to reduce blood pressure by 2.5 mm Hg in the approximately 50% of hypertensive U.S. black men who patronize these barbershops (2.2 million persons), we project that about 800 fewer myocardial infarctions, 550 fewer strokes, and 900 fewer deaths would occur in the first year alone,” the investigators noted.

Black-owned barbershops “are rapidly gaining traction as potential community partners for health promotion programs targeting hypertension as well as diabetes, prostate cancer, and other diseases that disproportionately affect black men,” the researchers said.

Such barbershops “are a cultural institution that draws a large and loyal male clientele and provides an open forum for discussion of numerous topics, including health, with influential peers.”

Dr. Victor and his colleagues conducted their study by offering free blood pressure screening to patrons of 17 barbershops representing four geographic sectors with sizeable black populations in the Barber-Assisted Reduction in Blood Pressure in Ethnic Residents (BARBER-1). Nine barbershops with 695 patrons who were found to have hypertension then were randomly allocated to the intervention, and eight barbershops with 602 patrons who had hypertension were randomly allocated to a comparison group.

Most of the barbershop clients were middle income.

The comparison group was not strictly a control group; patrons there underwent two BP screenings at baseline and received standard written explanations and recommendations for physician follow-up, because failing to advise them would have been unethical. The comparison barbershops also made available American Heart Association pamphlets entitled “High Blood Pressure in African Americans.”

For the intervention, barbers continually offered all male clients blood pressure checks along with their haircuts. They displayed large posters depicting authentic stories of other male hypertensive patrons of the same shop modeling treatment-seeking behavior, using the model's own words to tell the story. Barbers and other male patrons also discussed the issue conversationally.

The barbers were trained, equipped, and paid to conduct BP testing and interpret the results, with the main focus on encouraging clients who had positive results to consult a physician. They referred clients who had no physician to a nursing staff that then referred them to local physicians or safety-net clinics. Barbers also gave patrons found to be hypertensive a wallet-sized card for the physician to sign, documenting an office visit concerning hypertension.

The barbers were paid $3 for every recorded blood pressure they took, $10 for every referral they made to the nursing staff, and $50 for every BP card that clients returned to them with physicians' signatures. Patrons received free haircuts (a $12 value) for every BP card they returned with a physician's signature.

Overall, nearly half of the patrons who were screened had high blood pressure; 78% of them were already aware that they were hypertensive, and 69% said they were taking treatment for HT, yet only 38% had their blood pressure under control.

Barbers were able to measure blood pressure in three of every four patrons who had hypertension, and each hypertensive client averaged eight blood pressure checks during the 10-month study. “The barbers motivated 50% of their patrons with elevated BP readings to visit a physician,” the researchers said.

The rate of blood pressure control – the number of men who achieved blood pressure control during BARBER-1 – improved by about 10% in the comparison group, but improved by an additional and significant 8% in the intervention group. The intervention group also showed an absolute decrease of 2.5 mm Hg in systolic blood pressure compared with the control group, a secondary outcome of borderline significance, the investigators said (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.390]).

Major Finding: The rate of blood pressure control was a significant 8% higher in black men attending barbershops that participated in an active intervention than in those attending a comparison group of barbershops in Texas.

Data Source: BARBER-1, a cluster-randomized controlled trial assessing a barbershop-based health promotion program aimed at identifying hypertension in black men and referring them to a physician for treatment.

Disclosures: The National Heart, Lung, and Blood Institute, the Donald W. Reynolds Foundation, the Aetna Foundation Regional Health Disparity Program, Pfizer, Biovail, Cedars-Sinai Heart Institute, the Lincy Foundation, and the Robert Wood Johnson Foundation supported the trial. Dr. Victor reported ties to Pfizer and Biovail.

An outreach program in which barbers served as health educators – monitoring their black male clients' hypertension and referring them for medical treatment when necessary – improved the rate of blood pressure control by about 9% over 10 months, according to a report published online in the Archives of Internal Medicine

The intervention, which was tested in 17 black-owned barbershops in a single Texas county, motivated about half the hypertensive patrons at participating barbershops to see a physician, and reduced their systolic blood pressure by a mean of 2.5 mm Hg, said Dr. Ronald G. Victor of the University of Texas Southwest Medical Center, Dallas, and his associates.

“If the intervention could be implemented in the approximately 18,000 black-owned barbershops in the United States to reduce blood pressure by 2.5 mm Hg in the approximately 50% of hypertensive U.S. black men who patronize these barbershops (2.2 million persons), we project that about 800 fewer myocardial infarctions, 550 fewer strokes, and 900 fewer deaths would occur in the first year alone,” the investigators noted.

Black-owned barbershops “are rapidly gaining traction as potential community partners for health promotion programs targeting hypertension as well as diabetes, prostate cancer, and other diseases that disproportionately affect black men,” the researchers said.

Such barbershops “are a cultural institution that draws a large and loyal male clientele and provides an open forum for discussion of numerous topics, including health, with influential peers.”

Dr. Victor and his colleagues conducted their study by offering free blood pressure screening to patrons of 17 barbershops representing four geographic sectors with sizeable black populations in the Barber-Assisted Reduction in Blood Pressure in Ethnic Residents (BARBER-1). Nine barbershops with 695 patrons who were found to have hypertension then were randomly allocated to the intervention, and eight barbershops with 602 patrons who had hypertension were randomly allocated to a comparison group.

Most of the barbershop clients were middle income.

The comparison group was not strictly a control group; patrons there underwent two BP screenings at baseline and received standard written explanations and recommendations for physician follow-up, because failing to advise them would have been unethical. The comparison barbershops also made available American Heart Association pamphlets entitled “High Blood Pressure in African Americans.”

For the intervention, barbers continually offered all male clients blood pressure checks along with their haircuts. They displayed large posters depicting authentic stories of other male hypertensive patrons of the same shop modeling treatment-seeking behavior, using the model's own words to tell the story. Barbers and other male patrons also discussed the issue conversationally.

The barbers were trained, equipped, and paid to conduct BP testing and interpret the results, with the main focus on encouraging clients who had positive results to consult a physician. They referred clients who had no physician to a nursing staff that then referred them to local physicians or safety-net clinics. Barbers also gave patrons found to be hypertensive a wallet-sized card for the physician to sign, documenting an office visit concerning hypertension.

The barbers were paid $3 for every recorded blood pressure they took, $10 for every referral they made to the nursing staff, and $50 for every BP card that clients returned to them with physicians' signatures. Patrons received free haircuts (a $12 value) for every BP card they returned with a physician's signature.

Overall, nearly half of the patrons who were screened had high blood pressure; 78% of them were already aware that they were hypertensive, and 69% said they were taking treatment for HT, yet only 38% had their blood pressure under control.

Barbers were able to measure blood pressure in three of every four patrons who had hypertension, and each hypertensive client averaged eight blood pressure checks during the 10-month study. “The barbers motivated 50% of their patrons with elevated BP readings to visit a physician,” the researchers said.

The rate of blood pressure control – the number of men who achieved blood pressure control during BARBER-1 – improved by about 10% in the comparison group, but improved by an additional and significant 8% in the intervention group. The intervention group also showed an absolute decrease of 2.5 mm Hg in systolic blood pressure compared with the control group, a secondary outcome of borderline significance, the investigators said (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.390]).

The thrombopoietin mimetic romiplostim produced a higher rate of platelet response, a lower incidence of treatment failure, less need for splenectomy, and less bleeding than did a variety of standard-of-care therapies in patients with immune thrombocytopenia, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

At the same time, romiplostim produced fewer adverse effects than did the traditional treatments, leading to an improved quality of life, wrote Dr. David J. Kuter of Massachusetts General Hospital, Boston, and his associates.

To assess the efficacy and safety of romiplostim for immune thrombocytopenia, the investigators compared it with standard medical therapies in 234 patients treated at 85 medical centers throughout North America, Europe, and Australia. The study subjects were adults who had not undergone splenectomy and who had failed to respond to at least one traditional treatment. They were randomly assigned to receive open-label romiplostim (157 patients) or standard-of-care therapy (77 patients) for 1 year, and then followed for an additional 6-month safety monitoring period.

The study was designed and sponsored by Amgen, maker of romiplostim, and Amgen also gathered the data, conducted the statistical analyses, and interpreted the results.

Patients in both study groups were allowed to receive additional therapies, such as intravenous immune globulin or glucocorticoids, if they were deemed necessary.

The two main end points were the rate of treatment failure and the need for splenectomy, both of which were significantly better with romiplostim.

Treatment failure rates were 11% (18 of 157 subjects) with romiplostim and 30% with traditional therapies (23 of 77 subjects). Patients receiving romiplostim fared better with every component of treatment failure, including major bleeding episodes, lack of efficacy, and severe adverse effects. The time to treatment failure also was significantly longer with romiplostim.

The incidence of splenectomy was 9% (14 of 157 patients) with romiplostim and 36% (28 of 77 patients) with traditional therapies. The time to splenectomy also was "markedly prolonged" longer with romiplostim. "Avoidance of splenectomy may allow for a spontaneous remission in a substantial number of patients and may benefit those who are not surgical candidates," Dr. Kuter and his colleagues said (N. Engl. J. Med. 2010;363:1889-99).

Additional treatments were needed in significantly more subjects in the standard-of-care group (79%) than in the romiplostim group (44%).

Moreover, patients receiving romiplostim were 2.3 times more likely to show a platelet response than those in the standard-of-care group. The proportion of patients showing a platelet response ranged from 71% to 92% with romiplostim, compared with 26% to 51% with standard-of-care treatments. Also, the mean platelet count was higher with romiplostim for the entire duration of the study.

Treatment-related serious adverse events occurred in 5% of patients taking romiplostim and 8% of those taking standard-of-care therapies. Headache and fatigue were the most frequent mild adverse effects.

Adverse events considered to be "of interest" with thrombopoietin mimetics include bleeding, thrombosis, increased bone marrow reticulin, hematologic cancer, or myelodysplastic syndromes.

The rates of overall bleeding and serious bleeding both were significantly lower in the romiplostim group, and twice the proportion of patients receiving traditional therapies required transfusions (17% vs. 8%). The only hematologic cancers that developed were in the standard-of-care group. And there were no abnormal nonhematologic lab results and no neutralizing antibodies to romiplostin or thrombopoietin.

One patient in the romiplostim group showed bone marrow reticulin during the 6-month safety follow-up, but the level was within normal limits.

Both study groups showed improved quality of life after treatment, with the romiplostin group showing significantly greater benefits. However, the magnitude of this effect "is of uncertain clinical benefit," the investigators said.

"Our results show that romiplostim not only maintains platelet counts more effectively than standard medical therapies but also reduces the overall rate of treatment failure and the need for splenectomy," they noted.

This study was sponsored and designed by Amgen, which also gathered the data, conducted the statistical analyses, and interpreted the results. Dr. Kuter and his associates reported ties to numerous industry sources.

The thrombopoietin mimetic romiplostim produced a higher rate of platelet response, a lower incidence of treatment failure, less need for splenectomy, and less bleeding than did a variety of standard-of-care therapies in patients with immune thrombocytopenia, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

At the same time, romiplostim produced fewer adverse effects than did the traditional treatments, leading to an improved quality of life, wrote Dr. David J. Kuter of Massachusetts General Hospital, Boston, and his associates.

To assess the efficacy and safety of romiplostim for immune thrombocytopenia, the investigators compared it with standard medical therapies in 234 patients treated at 85 medical centers throughout North America, Europe, and Australia. The study subjects were adults who had not undergone splenectomy and who had failed to respond to at least one traditional treatment. They were randomly assigned to receive open-label romiplostim (157 patients) or standard-of-care therapy (77 patients) for 1 year, and then followed for an additional 6-month safety monitoring period.

The study was designed and sponsored by Amgen, maker of romiplostim, and Amgen also gathered the data, conducted the statistical analyses, and interpreted the results.

Patients in both study groups were allowed to receive additional therapies, such as intravenous immune globulin or glucocorticoids, if they were deemed necessary.

The two main end points were the rate of treatment failure and the need for splenectomy, both of which were significantly better with romiplostim.

Treatment failure rates were 11% (18 of 157 subjects) with romiplostim and 30% with traditional therapies (23 of 77 subjects). Patients receiving romiplostim fared better with every component of treatment failure, including major bleeding episodes, lack of efficacy, and severe adverse effects. The time to treatment failure also was significantly longer with romiplostim.

The incidence of splenectomy was 9% (14 of 157 patients) with romiplostim and 36% (28 of 77 patients) with traditional therapies. The time to splenectomy also was "markedly prolonged" longer with romiplostim. "Avoidance of splenectomy may allow for a spontaneous remission in a substantial number of patients and may benefit those who are not surgical candidates," Dr. Kuter and his colleagues said (N. Engl. J. Med. 2010;363:1889-99).

Additional treatments were needed in significantly more subjects in the standard-of-care group (79%) than in the romiplostim group (44%).

Moreover, patients receiving romiplostim were 2.3 times more likely to show a platelet response than those in the standard-of-care group. The proportion of patients showing a platelet response ranged from 71% to 92% with romiplostim, compared with 26% to 51% with standard-of-care treatments. Also, the mean platelet count was higher with romiplostim for the entire duration of the study.

Treatment-related serious adverse events occurred in 5% of patients taking romiplostim and 8% of those taking standard-of-care therapies. Headache and fatigue were the most frequent mild adverse effects.

Adverse events considered to be "of interest" with thrombopoietin mimetics include bleeding, thrombosis, increased bone marrow reticulin, hematologic cancer, or myelodysplastic syndromes.

The rates of overall bleeding and serious bleeding both were significantly lower in the romiplostim group, and twice the proportion of patients receiving traditional therapies required transfusions (17% vs. 8%). The only hematologic cancers that developed were in the standard-of-care group. And there were no abnormal nonhematologic lab results and no neutralizing antibodies to romiplostin or thrombopoietin.

One patient in the romiplostim group showed bone marrow reticulin during the 6-month safety follow-up, but the level was within normal limits.

Both study groups showed improved quality of life after treatment, with the romiplostin group showing significantly greater benefits. However, the magnitude of this effect "is of uncertain clinical benefit," the investigators said.

"Our results show that romiplostim not only maintains platelet counts more effectively than standard medical therapies but also reduces the overall rate of treatment failure and the need for splenectomy," they noted.

This study was sponsored and designed by Amgen, which also gathered the data, conducted the statistical analyses, and interpreted the results. Dr. Kuter and his associates reported ties to numerous industry sources.

The thrombopoietin mimetic romiplostim produced a higher rate of platelet response, a lower incidence of treatment failure, less need for splenectomy, and less bleeding than did a variety of standard-of-care therapies in patients with immune thrombocytopenia, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

At the same time, romiplostim produced fewer adverse effects than did the traditional treatments, leading to an improved quality of life, wrote Dr. David J. Kuter of Massachusetts General Hospital, Boston, and his associates.

To assess the efficacy and safety of romiplostim for immune thrombocytopenia, the investigators compared it with standard medical therapies in 234 patients treated at 85 medical centers throughout North America, Europe, and Australia. The study subjects were adults who had not undergone splenectomy and who had failed to respond to at least one traditional treatment. They were randomly assigned to receive open-label romiplostim (157 patients) or standard-of-care therapy (77 patients) for 1 year, and then followed for an additional 6-month safety monitoring period.

The study was designed and sponsored by Amgen, maker of romiplostim, and Amgen also gathered the data, conducted the statistical analyses, and interpreted the results.

Patients in both study groups were allowed to receive additional therapies, such as intravenous immune globulin or glucocorticoids, if they were deemed necessary.

The two main end points were the rate of treatment failure and the need for splenectomy, both of which were significantly better with romiplostim.

Treatment failure rates were 11% (18 of 157 subjects) with romiplostim and 30% with traditional therapies (23 of 77 subjects). Patients receiving romiplostim fared better with every component of treatment failure, including major bleeding episodes, lack of efficacy, and severe adverse effects. The time to treatment failure also was significantly longer with romiplostim.

The incidence of splenectomy was 9% (14 of 157 patients) with romiplostim and 36% (28 of 77 patients) with traditional therapies. The time to splenectomy also was "markedly prolonged" longer with romiplostim. "Avoidance of splenectomy may allow for a spontaneous remission in a substantial number of patients and may benefit those who are not surgical candidates," Dr. Kuter and his colleagues said (N. Engl. J. Med. 2010;363:1889-99).

Additional treatments were needed in significantly more subjects in the standard-of-care group (79%) than in the romiplostim group (44%).

Moreover, patients receiving romiplostim were 2.3 times more likely to show a platelet response than those in the standard-of-care group. The proportion of patients showing a platelet response ranged from 71% to 92% with romiplostim, compared with 26% to 51% with standard-of-care treatments. Also, the mean platelet count was higher with romiplostim for the entire duration of the study.

Treatment-related serious adverse events occurred in 5% of patients taking romiplostim and 8% of those taking standard-of-care therapies. Headache and fatigue were the most frequent mild adverse effects.

Adverse events considered to be "of interest" with thrombopoietin mimetics include bleeding, thrombosis, increased bone marrow reticulin, hematologic cancer, or myelodysplastic syndromes.

The rates of overall bleeding and serious bleeding both were significantly lower in the romiplostim group, and twice the proportion of patients receiving traditional therapies required transfusions (17% vs. 8%). The only hematologic cancers that developed were in the standard-of-care group. And there were no abnormal nonhematologic lab results and no neutralizing antibodies to romiplostin or thrombopoietin.

One patient in the romiplostim group showed bone marrow reticulin during the 6-month safety follow-up, but the level was within normal limits.

Both study groups showed improved quality of life after treatment, with the romiplostin group showing significantly greater benefits. However, the magnitude of this effect "is of uncertain clinical benefit," the investigators said.

"Our results show that romiplostim not only maintains platelet counts more effectively than standard medical therapies but also reduces the overall rate of treatment failure and the need for splenectomy," they noted.

This study was sponsored and designed by Amgen, which also gathered the data, conducted the statistical analyses, and interpreted the results. Dr. Kuter and his associates reported ties to numerous industry sources.

Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow’s-milk–based formula during infancy, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

Photo credit: Jaimie Duplass/Fotalia.com

This indicates that "a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible," said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.

Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.

The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow’s-milk–based formula made to smell and taste like the intervention formula.

Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.

Blood samples were obtained periodically to test for five disease-related autoantibodies: islet-cell antibodies; insulin antibodies; and antibodies to glutamic acid decarboxylase (GAD), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 (ZnT8).

The intervention formula was associated with a significant decrease in risk of seropositivity for islet-cell antibodies, IA-2 autoantibodies, or to at least one of the five autoantibodies assessed, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).

By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to demonstrate significance of this measure, they added.

Although preliminary data from small clinical studies and animal studies have suggested that "complex foreign-protein diets during weaning may play a deleterious role in the process leading to autoimmune diabetes," the mechanism is not yet known. "We speculate that potential mechanisms may involve reduced gut permeability, induction of the maturation of regulatory T cells in the gut-associated lymphoid tissue, modification of the gut microflora, or some combination of these," the investigators said.

If further study confirms that highly hydrolyzed formula safely protects high-risk children from developing type 1 diabetes, "a next step might be to expand the intervention to a wider infant population, since 83%-98% of children with newly diagnosed type 1 diabetes are from the general population," Dr. Knip and his associates added.

This strategy could be a relatively easily implemented public health measure, they said.

This study was funded by the Academy of Finland, the European Commission, the Juvenile Diabetes Foundation International, the Novo Nordisk Foundation, and several other nonindustry sources. Infant formulas were provided by Mead Johnson Nutrition, which had no role in the study design, collection or analysis of data, or preparation of the manuscript. Dr. Knip’s associate reported receiving a grant from the Foundation for Paediatric Research. Dr. Knip and the other associates reported no conflicts of interest.

Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow’s-milk–based formula during infancy, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

Photo credit: Jaimie Duplass/Fotalia.com

This indicates that "a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible," said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.

Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.

The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow’s-milk–based formula made to smell and taste like the intervention formula.

Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.

Blood samples were obtained periodically to test for five disease-related autoantibodies: islet-cell antibodies; insulin antibodies; and antibodies to glutamic acid decarboxylase (GAD), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 (ZnT8).

The intervention formula was associated with a significant decrease in risk of seropositivity for islet-cell antibodies, IA-2 autoantibodies, or to at least one of the five autoantibodies assessed, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).

By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to demonstrate significance of this measure, they added.

Although preliminary data from small clinical studies and animal studies have suggested that "complex foreign-protein diets during weaning may play a deleterious role in the process leading to autoimmune diabetes," the mechanism is not yet known. "We speculate that potential mechanisms may involve reduced gut permeability, induction of the maturation of regulatory T cells in the gut-associated lymphoid tissue, modification of the gut microflora, or some combination of these," the investigators said.

If further study confirms that highly hydrolyzed formula safely protects high-risk children from developing type 1 diabetes, "a next step might be to expand the intervention to a wider infant population, since 83%-98% of children with newly diagnosed type 1 diabetes are from the general population," Dr. Knip and his associates added.

This strategy could be a relatively easily implemented public health measure, they said.

This study was funded by the Academy of Finland, the European Commission, the Juvenile Diabetes Foundation International, the Novo Nordisk Foundation, and several other nonindustry sources. Infant formulas were provided by Mead Johnson Nutrition, which had no role in the study design, collection or analysis of data, or preparation of the manuscript. Dr. Knip’s associate reported receiving a grant from the Foundation for Paediatric Research. Dr. Knip and the other associates reported no conflicts of interest.

Children at risk for type 1 diabetes showed fewer signs of beta-cell autoimmunity for up to 10 years if they were fed a highly hydrolyzed casein formula rather than conventional cow’s-milk–based formula during infancy, according to a report in the Nov. 11 issue of the New England Journal of Medicine.

Photo credit: Jaimie Duplass/Fotalia.com

This indicates that "a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible," said Dr. Mikael Knip of the University of Helsinki, Finland, and his associates.

Their pilot study – the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) – was not sufficiently powered to render a definitive conclusion about preventing progression to overt type 1 diabetes. However, a larger ongoing TRIGR study is now underway in 15 countries and is designed to address that issue, the investigators noted.

The pilot study involved 230 neonates born at 15 Finnish hospitals between 1995 and 1997 whose HLA genotypes showed susceptibility to type 1 diabetes and who had at least one first-degree relative with the disorder. The newborns were randomly assigned in a double-blind fashion to receive for at least 6 months either an extensively hydrolyzed casein-based formula (Nutramigen) or a control cow’s-milk–based formula made to smell and taste like the intervention formula.

Both formulas were offered only when breast milk was unavailable. Breast-feeding was encouraged, and mothers breast-fed at their own discretion and without modifying their diets.

Blood samples were obtained periodically to test for five disease-related autoantibodies: islet-cell antibodies; insulin antibodies; and antibodies to glutamic acid decarboxylase (GAD), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 (ZnT8).

The intervention formula was associated with a significant decrease in risk of seropositivity for islet-cell antibodies, IA-2 autoantibodies, or to at least one of the five autoantibodies assessed, Dr. Knip and his colleagues said (N. Engl. J. Med. 2010;363:1900-8).

By 10 years of age, 6% of children in the intervention group and 8% of those in the control group developed type 1 diabetes. This difference was nonsignificant, but the study was not designed to demonstrate significance of this measure, they added.

Although preliminary data from small clinical studies and animal studies have suggested that "complex foreign-protein diets during weaning may play a deleterious role in the process leading to autoimmune diabetes," the mechanism is not yet known. "We speculate that potential mechanisms may involve reduced gut permeability, induction of the maturation of regulatory T cells in the gut-associated lymphoid tissue, modification of the gut microflora, or some combination of these," the investigators said.

If further study confirms that highly hydrolyzed formula safely protects high-risk children from developing type 1 diabetes, "a next step might be to expand the intervention to a wider infant population, since 83%-98% of children with newly diagnosed type 1 diabetes are from the general population," Dr. Knip and his associates added.

This strategy could be a relatively easily implemented public health measure, they said.

This study was funded by the Academy of Finland, the European Commission, the Juvenile Diabetes Foundation International, the Novo Nordisk Foundation, and several other nonindustry sources. Infant formulas were provided by Mead Johnson Nutrition, which had no role in the study design, collection or analysis of data, or preparation of the manuscript. Dr. Knip’s associate reported receiving a grant from the Foundation for Paediatric Research. Dr. Knip and the other associates reported no conflicts of interest.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Hospitals’ surveillance techniques for central-line–associated bloodstream infections may vary so much that attempts to compare the results among medical centers are likely to be inaccurate, according to a Nov. 10 report in JAMA.

Such bloodstream infection rates "are considered a key patient safety measure because such infections are frequent, lead to poor patient outcomes, are costly to the medical system, and are preventable," said Dr. Michael Y. Lin of Rush University Medical Center, Chicago, and his associates.

"Publishing infection rates on hospital report cards, which is increasingly required by regulatory agencies, is intended to facilitate interhospital comparisons that inform health care consumers and provide incentive for hospitals to prevent infections," the study authors noted. But such comparisons are [valid only] if the surveillance methods are somewhat uniform and the results of hospitals’ internal reviews can be confirmed by external measures, they remarked. In addition, very few studies have examined the issue.

Most hospitals designate an employee – usually a registered nurse, medical technologist, or microbiologist trained in infection control – as their infection preventionist, who is in charge of surveillance and reporting of central-line–associated bloodstream infections, as well as other nosocomial infections. To assure a degree of uniformity, that specialist typically uses case definitions and criteria published by the Centers for Disease Control and Prevention.

But surveillance, particularly case finding, is time consuming and depends largely on the effort this individual puts into the job, the researchers cautioned. It also entails subjective factors such as judging whether a case of bacteremia stems from a central line or from some other source, or judging whether cultures that show a common skin organism denote a true infection or contamination of the sample, Dr. Lin and his colleagues said.

"The recent development of computer algorithms for central-line–associated bloodstream infection surveillance provides an opportunity to establish an objective reference standard with which to benchmark" those techniques, they noted.

Dr. Lin and his associates retrospectively studied surveillance of central-line–associated bloodstream infections in 20 intensive care units at four Midwestern academic medical centers, comparing the results of surveillance using computer algorithms (intended to cut down on rater subjectivity) with those of traditional surveillance by an infection preventionist (JAMA 2010;304:2035-41).

The retrospective review included medical, surgical, neurosurgical, cardiac, oncologic, cardiothoracic surgical, burn, bone marrow transplant, and trauma ICUs. The researchers assessed 41 12-month periods representing 241,518 patient-days and 165,963 central-line-days.

"We hypothesized that although we would find differences in the absolute infection rates estimated by infection-preventionist surveillance as opposed to computer algorithm surveillance, we would find reasonable and uniform ecologic correlation between the two methods," the investigators said. "Instead, we found weak overall correlation between the two methods and, importantly, variable correlation when stratified by medical center."

The overall median rate of bloodstream infection, as measured by infection preventionists, was 3.3 infections/1,000 central-line days. In contrast, the median rate as measured using the computer algorithm was a significantly higher: 9.0/1,000 central-line days.

Just as important, the rate of infection as measured by infection preventionists varied significantly by hospital. "Our findings suggest that there is local variation in central-line–associated bloodstream infection surveillance performance at different medical centers, raising concern for the validity of interinstitutional rate comparisons," they noted.

In recent years, public reporting of hospital infection rates increasingly has been touted as a way to compare patient safety among different institutions, the investigators said. In the United States, about one-quarter of all states require reporting of central-line–associated bloodstream infection rates from ICUs – data that patients, advocacy groups, and regulators use to compare hospitals. "Furthermore, hospital reimbursement is increasingly dependent on reported rates," Dr. Lin and his associates said.

"Our study highlights the potential fallibility of traditional surveillance methods using partially subjective criteria," they explained, "and underscores the need for cautious interpretation of these results until more reliable measures or validation against objective measures can routinely be performed."

In particular, infection preventionists can differ in their classification of ambiguous cases. Differences also exist at the institution level, such as when hospitals use different culturing practices, different methods of medical documentation, and different degrees of institutional oversight of their surveillance programs, the researchers noted.

The Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.

Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.

The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.

"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.

The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.

Among the new consensus statement’s findings are the following:

• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.

• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.

• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.

• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.

• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.

• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.

• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.

Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).

Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."

"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.

The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.