Mary Ann Moon

More than half of select patients with advanced non–small-cell lung cancers responded to treatment with crizotinib, according to findings of a phase I multicenter clinical trial reported in the Oct. 28 issue of the New England Journal of Medicine.

Crizotinib inhibits the anaplastic lymphoma kinase (ALK) gene’s receptor, tyrosine kinase, which has been linked to several types of cancer.

In a group of 82 patients, many of whom had undergone numerous anticancer therapies for advanced ALK-positive tumors, the overall partial and complete response rate was 57%, and disease stabilized in an additional 33%. These results are "impressive" compared with the approximately 10% response rate seen in similar cancers treated with second-line multiagent chemotherapy, said Dr. Eunice L. Kwak of Massachusetts General Hospital Cancer Center, Boston, and her associates.

The probability of 6-month progression-free survival was estimated to be 72% with crizotinib therapy, compared with a rate of 27% for similar tumors treated with second-line chemotherapy.

The dose of oral crizotinib was escalated from 50 mg once daily to 300 mg twice daily. Dose-limiting fatigue was noted at this level, so the maximal dose was cut back to 250 mg twice daily.

A total of 46 patients met RECIST criteria for a partial response and 1 for a complete response to the drug, for an overall response rate of 57%. An additional 27 patients met criteria for stable disease.

Treatment response was quite rapid, with a disease-control rate of 87% at 8 weeks.

The rapid response to crizotinib "suggests that ALK-positive tumors constitute a second genetically defined subgroup of oncogene-driven lung cancer that is highly susceptible to targeted therapy," the investigators noted.

Nausea and diarrhea were the most common adverse effects. Thirty-four patients (41%) reported mild visual disturbances, but no abnormalities were detected on ophthalmologic examination.

Four patients showed elevated alanine aminotransferase (ALT) levels and 5 showed elevated aspartate amino transferase (AST) levels, all of which reverted to normal when crizotinib was discontinued. Four of these patients were able to resume the treatment at a lower dose without recurrence of this toxicity.

A total of 63 patients (77%) continued to receive crizotinib after the conclusion of the study and continue to be followed.

These findings demonstrate the importance and feasibility of genotyping to individualize treatment. They also show that non–small-cell lung tumors with ALK rearrangements – which occurred in approximately 5% of the patients screened for participation in this trial – are highly sensitive to ALK kinase inhibition, Dr. Kwak and her colleagues said (N. Engl. J. Med. 2010;363:1693-703).

Two separate case reports published in the same issue of the journal further delineated outcomes with crizotinib therapy.

In the first, a 28-year-old man with large tumor nodules in one lung, multiple enlarged lymph nodes in the mediastinum, atelectasis, and massive effusion in the right pleural cavity showed a marked initial response to the crizotinib within 1 week. However, after 5 months of treatment his tumor "abruptly started to grow again, resulting in a rapid expansion of the pleural effusion and the development of tumors in both lungs," said Dr. Young Lim Choi of Jichi Medical University, Tochigi, Japan, and associates.

Suspecting that the cancer may have acquired genetic changes that conferred resistance to crizotinib, the researchers identified in sputum and effusion specimens two de novo mutations within the kinase domain of the ALK gene. "We do not know whether the resistant clones were present initially or developed secondarily, during treatment," they noted (N. Engl. J. Med. 2010;363:1734-9).

It is likely that an as-yet unidentified mechanism is present in oncogenic tyrosine kinases, which facilitates the development of further mutations that confer resistance to many ALK inhibitors. Further research should shed light on this process and lead to the development of next-generation ALK inhibitors that address the mutations and the resistance they confer, Dr. Choi and colleagues added.

In the second case study, two patients with another type of cancer – inflammatory myofibroblastic tumors (IMTs) – were given crizotinib empirically. It was hoped that the drug would show activity in these patients because approximately half of IMTs carry rearrangements of the ALK gene, said Dr. James E. Butrynski of the Dana-Farber Cancer Institute, Boston, and his associates.

The first patient was a 44-year-old man whose extensive peritoneal and mesenteric cancer had recurred after surgical excision; peritoneal perfusion with combined cisplatin, doxorubicin, and mitomycin C; further treatment with doxorubicin and ifosfamide; and maintenance therapy with imatinib. The patient responded to daily crizotinib beginning in December 2008 and has maintained complete radiographic remission until press time.

The second patient, a 21-year-old man with IMT involving the stomach, large intestine, gall bladder, and spleen, did not respond to crizotinib, instead showing continued disease progression.

Further analysis showed that the tumor in patient 1 had ALK rearrangements while that in patient 2 did not. Together, these two cases indicate that crizotinib’s mechanism of action is to disrupt mutations in ALK signaling pathways that certain cancers require for continued growth. The drug is effective only in those IMTs with ALK rearrangements (N. Engl. J. Med. 2010;363:1727-33).

"Patient 1 continues to have an excellent performance status and only mild side effects, supporting the tolerability of the long-term administration of crizotinib," Dr. Butrynski and his colleagues added.

Dr. Kwak’s study was supported by Pfizer, Massachusetts General Hospital Cancer Center, the Aid for Cancer Research Foundation, National Cancer Institute, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, National Institutes of Health, American Society for Clinical Oncology Cancer Foundation, Memorial Sloan-Kettering Cancer Center, and the University of Colorado Cancer Center. Dr. Kwak and her associates reported numerous financial ties to 67 drug, device, and technology companies.

Dr. Choi’s study was supported in part by the Ministry of Health, Labor, and Welfare of Japan, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Japan Society for the Promotion of Science. Dr. Choi reported ties to Astellas Pharmaceuticals, and associates reported ties to 15 drug, device, and technology companies.

Dr. Butrynski’s study was supported by Pfizer, the National Institutes of Health, the National Cancer Institute–American Society of Clinical Oncology Cancer Foundation, and Cycle for Survival. His associates reported ties to 29 drug, device, and technology companies.

More than half of select patients with advanced non–small-cell lung cancers responded to treatment with crizotinib, according to findings of a phase I multicenter clinical trial reported in the Oct. 28 issue of the New England Journal of Medicine.

Crizotinib inhibits the anaplastic lymphoma kinase (ALK) gene’s receptor, tyrosine kinase, which has been linked to several types of cancer.

In a group of 82 patients, many of whom had undergone numerous anticancer therapies for advanced ALK-positive tumors, the overall partial and complete response rate was 57%, and disease stabilized in an additional 33%. These results are "impressive" compared with the approximately 10% response rate seen in similar cancers treated with second-line multiagent chemotherapy, said Dr. Eunice L. Kwak of Massachusetts General Hospital Cancer Center, Boston, and her associates.

The probability of 6-month progression-free survival was estimated to be 72% with crizotinib therapy, compared with a rate of 27% for similar tumors treated with second-line chemotherapy.

The dose of oral crizotinib was escalated from 50 mg once daily to 300 mg twice daily. Dose-limiting fatigue was noted at this level, so the maximal dose was cut back to 250 mg twice daily.

A total of 46 patients met RECIST criteria for a partial response and 1 for a complete response to the drug, for an overall response rate of 57%. An additional 27 patients met criteria for stable disease.

Treatment response was quite rapid, with a disease-control rate of 87% at 8 weeks.

The rapid response to crizotinib "suggests that ALK-positive tumors constitute a second genetically defined subgroup of oncogene-driven lung cancer that is highly susceptible to targeted therapy," the investigators noted.

Nausea and diarrhea were the most common adverse effects. Thirty-four patients (41%) reported mild visual disturbances, but no abnormalities were detected on ophthalmologic examination.

Four patients showed elevated alanine aminotransferase (ALT) levels and 5 showed elevated aspartate amino transferase (AST) levels, all of which reverted to normal when crizotinib was discontinued. Four of these patients were able to resume the treatment at a lower dose without recurrence of this toxicity.

A total of 63 patients (77%) continued to receive crizotinib after the conclusion of the study and continue to be followed.

These findings demonstrate the importance and feasibility of genotyping to individualize treatment. They also show that non–small-cell lung tumors with ALK rearrangements – which occurred in approximately 5% of the patients screened for participation in this trial – are highly sensitive to ALK kinase inhibition, Dr. Kwak and her colleagues said (N. Engl. J. Med. 2010;363:1693-703).

Two separate case reports published in the same issue of the journal further delineated outcomes with crizotinib therapy.

In the first, a 28-year-old man with large tumor nodules in one lung, multiple enlarged lymph nodes in the mediastinum, atelectasis, and massive effusion in the right pleural cavity showed a marked initial response to the crizotinib within 1 week. However, after 5 months of treatment his tumor "abruptly started to grow again, resulting in a rapid expansion of the pleural effusion and the development of tumors in both lungs," said Dr. Young Lim Choi of Jichi Medical University, Tochigi, Japan, and associates.

Suspecting that the cancer may have acquired genetic changes that conferred resistance to crizotinib, the researchers identified in sputum and effusion specimens two de novo mutations within the kinase domain of the ALK gene. "We do not know whether the resistant clones were present initially or developed secondarily, during treatment," they noted (N. Engl. J. Med. 2010;363:1734-9).

It is likely that an as-yet unidentified mechanism is present in oncogenic tyrosine kinases, which facilitates the development of further mutations that confer resistance to many ALK inhibitors. Further research should shed light on this process and lead to the development of next-generation ALK inhibitors that address the mutations and the resistance they confer, Dr. Choi and colleagues added.

In the second case study, two patients with another type of cancer – inflammatory myofibroblastic tumors (IMTs) – were given crizotinib empirically. It was hoped that the drug would show activity in these patients because approximately half of IMTs carry rearrangements of the ALK gene, said Dr. James E. Butrynski of the Dana-Farber Cancer Institute, Boston, and his associates.

The first patient was a 44-year-old man whose extensive peritoneal and mesenteric cancer had recurred after surgical excision; peritoneal perfusion with combined cisplatin, doxorubicin, and mitomycin C; further treatment with doxorubicin and ifosfamide; and maintenance therapy with imatinib. The patient responded to daily crizotinib beginning in December 2008 and has maintained complete radiographic remission until press time.

The second patient, a 21-year-old man with IMT involving the stomach, large intestine, gall bladder, and spleen, did not respond to crizotinib, instead showing continued disease progression.

Further analysis showed that the tumor in patient 1 had ALK rearrangements while that in patient 2 did not. Together, these two cases indicate that crizotinib’s mechanism of action is to disrupt mutations in ALK signaling pathways that certain cancers require for continued growth. The drug is effective only in those IMTs with ALK rearrangements (N. Engl. J. Med. 2010;363:1727-33).

"Patient 1 continues to have an excellent performance status and only mild side effects, supporting the tolerability of the long-term administration of crizotinib," Dr. Butrynski and his colleagues added.

Dr. Kwak’s study was supported by Pfizer, Massachusetts General Hospital Cancer Center, the Aid for Cancer Research Foundation, National Cancer Institute, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, National Institutes of Health, American Society for Clinical Oncology Cancer Foundation, Memorial Sloan-Kettering Cancer Center, and the University of Colorado Cancer Center. Dr. Kwak and her associates reported numerous financial ties to 67 drug, device, and technology companies.

Dr. Choi’s study was supported in part by the Ministry of Health, Labor, and Welfare of Japan, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Japan Society for the Promotion of Science. Dr. Choi reported ties to Astellas Pharmaceuticals, and associates reported ties to 15 drug, device, and technology companies.

Dr. Butrynski’s study was supported by Pfizer, the National Institutes of Health, the National Cancer Institute–American Society of Clinical Oncology Cancer Foundation, and Cycle for Survival. His associates reported ties to 29 drug, device, and technology companies.

More than half of select patients with advanced non–small-cell lung cancers responded to treatment with crizotinib, according to findings of a phase I multicenter clinical trial reported in the Oct. 28 issue of the New England Journal of Medicine.

Crizotinib inhibits the anaplastic lymphoma kinase (ALK) gene’s receptor, tyrosine kinase, which has been linked to several types of cancer.

In a group of 82 patients, many of whom had undergone numerous anticancer therapies for advanced ALK-positive tumors, the overall partial and complete response rate was 57%, and disease stabilized in an additional 33%. These results are "impressive" compared with the approximately 10% response rate seen in similar cancers treated with second-line multiagent chemotherapy, said Dr. Eunice L. Kwak of Massachusetts General Hospital Cancer Center, Boston, and her associates.

The probability of 6-month progression-free survival was estimated to be 72% with crizotinib therapy, compared with a rate of 27% for similar tumors treated with second-line chemotherapy.

The dose of oral crizotinib was escalated from 50 mg once daily to 300 mg twice daily. Dose-limiting fatigue was noted at this level, so the maximal dose was cut back to 250 mg twice daily.

A total of 46 patients met RECIST criteria for a partial response and 1 for a complete response to the drug, for an overall response rate of 57%. An additional 27 patients met criteria for stable disease.

Treatment response was quite rapid, with a disease-control rate of 87% at 8 weeks.

The rapid response to crizotinib "suggests that ALK-positive tumors constitute a second genetically defined subgroup of oncogene-driven lung cancer that is highly susceptible to targeted therapy," the investigators noted.

Nausea and diarrhea were the most common adverse effects. Thirty-four patients (41%) reported mild visual disturbances, but no abnormalities were detected on ophthalmologic examination.

Four patients showed elevated alanine aminotransferase (ALT) levels and 5 showed elevated aspartate amino transferase (AST) levels, all of which reverted to normal when crizotinib was discontinued. Four of these patients were able to resume the treatment at a lower dose without recurrence of this toxicity.

A total of 63 patients (77%) continued to receive crizotinib after the conclusion of the study and continue to be followed.

These findings demonstrate the importance and feasibility of genotyping to individualize treatment. They also show that non–small-cell lung tumors with ALK rearrangements – which occurred in approximately 5% of the patients screened for participation in this trial – are highly sensitive to ALK kinase inhibition, Dr. Kwak and her colleagues said (N. Engl. J. Med. 2010;363:1693-703).

Two separate case reports published in the same issue of the journal further delineated outcomes with crizotinib therapy.

In the first, a 28-year-old man with large tumor nodules in one lung, multiple enlarged lymph nodes in the mediastinum, atelectasis, and massive effusion in the right pleural cavity showed a marked initial response to the crizotinib within 1 week. However, after 5 months of treatment his tumor "abruptly started to grow again, resulting in a rapid expansion of the pleural effusion and the development of tumors in both lungs," said Dr. Young Lim Choi of Jichi Medical University, Tochigi, Japan, and associates.

Suspecting that the cancer may have acquired genetic changes that conferred resistance to crizotinib, the researchers identified in sputum and effusion specimens two de novo mutations within the kinase domain of the ALK gene. "We do not know whether the resistant clones were present initially or developed secondarily, during treatment," they noted (N. Engl. J. Med. 2010;363:1734-9).

It is likely that an as-yet unidentified mechanism is present in oncogenic tyrosine kinases, which facilitates the development of further mutations that confer resistance to many ALK inhibitors. Further research should shed light on this process and lead to the development of next-generation ALK inhibitors that address the mutations and the resistance they confer, Dr. Choi and colleagues added.

In the second case study, two patients with another type of cancer – inflammatory myofibroblastic tumors (IMTs) – were given crizotinib empirically. It was hoped that the drug would show activity in these patients because approximately half of IMTs carry rearrangements of the ALK gene, said Dr. James E. Butrynski of the Dana-Farber Cancer Institute, Boston, and his associates.

The first patient was a 44-year-old man whose extensive peritoneal and mesenteric cancer had recurred after surgical excision; peritoneal perfusion with combined cisplatin, doxorubicin, and mitomycin C; further treatment with doxorubicin and ifosfamide; and maintenance therapy with imatinib. The patient responded to daily crizotinib beginning in December 2008 and has maintained complete radiographic remission until press time.

The second patient, a 21-year-old man with IMT involving the stomach, large intestine, gall bladder, and spleen, did not respond to crizotinib, instead showing continued disease progression.

Further analysis showed that the tumor in patient 1 had ALK rearrangements while that in patient 2 did not. Together, these two cases indicate that crizotinib’s mechanism of action is to disrupt mutations in ALK signaling pathways that certain cancers require for continued growth. The drug is effective only in those IMTs with ALK rearrangements (N. Engl. J. Med. 2010;363:1727-33).

"Patient 1 continues to have an excellent performance status and only mild side effects, supporting the tolerability of the long-term administration of crizotinib," Dr. Butrynski and his colleagues added.

Dr. Kwak’s study was supported by Pfizer, Massachusetts General Hospital Cancer Center, the Aid for Cancer Research Foundation, National Cancer Institute, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, National Institutes of Health, American Society for Clinical Oncology Cancer Foundation, Memorial Sloan-Kettering Cancer Center, and the University of Colorado Cancer Center. Dr. Kwak and her associates reported numerous financial ties to 67 drug, device, and technology companies.

Dr. Choi’s study was supported in part by the Ministry of Health, Labor, and Welfare of Japan, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Japan Society for the Promotion of Science. Dr. Choi reported ties to Astellas Pharmaceuticals, and associates reported ties to 15 drug, device, and technology companies.

Dr. Butrynski’s study was supported by Pfizer, the National Institutes of Health, the National Cancer Institute–American Society of Clinical Oncology Cancer Foundation, and Cycle for Survival. His associates reported ties to 29 drug, device, and technology companies.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.

The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).

Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.

The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.

The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.

Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.

Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.

Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.

Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.

“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.

They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.

These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.

As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.

This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.

The investigators had no disclosures to report.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Carrying just one reduced-function CYP2C19 allele conveys a poor response to clopidogrel in patients undergoing percutaneous coronary intervention, significantly raising the risk of adverse cardiovascular events, especially stent thrombosis, according to a meta-analysis reported in the Oct. 27 issue of JAMA.

“CYP2C19 genetic information identifies approximately 30% of the population who may be less likely to be protected from recurrent ischemic events after PCI despite treatment with standard doses of clopidogrel,” said Dr. Jessica L. Mega of Brigham and Women’s Hospital, Boston, and her associates.

Certain variants of the CYP2C19 gene, which encodes for cytochrome P450 isoenzymes, are known to diminish the platelet inhibition effect of clopidogrel. However, “there is not consensus as to whether the diminished pharmacologic response translates into worse clinical outcomes and whether the proposed increased risk of adverse cardiovascular outcomes requires two reduced-function CYP2C19 alleles (present in approximately 2% of the white population) or can be seen with just one (present in approximately 26% of the white population),” Dr. Mega and her colleagues said.

To examine the association between CYP2C19 genotype and clinical outcomes, the researchers performed a collaborative meta-analysis with investigators in nine cohort studies and clinical trials of the issue. Authors of each study provided data on 9,685 subjects’ genotypic status and on overall outcomes. More than 91% of the study subjects received clopidogrel because they were undergoing PCI, and the remainder did so for the treatment of acute coronary syndromes.

A total of 72% of the subjects had no reduced-function CYP2C19 alleles, 26% had one reduced-function allele, and 2% had two reduced-function alleles.

Overall, 863 of the 9,685 study subjects developed the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. Carriers of either one or two reduced-function alleles were significantly more likely to achieve this end point than were noncarriers (hazard ratio, 1.57). More specifically, carriers of two reduced-function alleles had a significantly higher risk for the composite end point (HR 1.76) than did those with one such allele (HR 1.55), compared with noncarriers.

Regarding the individual components of the composite end point, carriers of one or two reduced-function CYP2C19 alleles had hazard ratios of 1.84 for cardiovascular death, 1.45 for nonfatal MI, and 1.73 for stroke, compared with noncarriers.

A particularly strong association was seen between the genotype and stent thrombosis. In the subset of 5,894 patients who received stents during PCI, 84 developed stent thrombosis, predominantly in the early postoperative period. Compared with noncarriers, carriers of one reduced-function allele had a hazard ratio of 2.67 and carriers of two reduced-function alleles had a hazard ratio of 3.97 for stent thrombosis.

“Even partial reductions in the antiplatelet effect of clopidogrel could translate into a several-fold increase in the risk of major adverse cardiovascular outcomes,” Dr. Mega and her associates said (JAMA 2010;304:1821-30).

The findings of this meta-analysis support the theory that reduced-function variants of the CYP2C19 gene exert their blunting effect on clopidogrel by reducing bioactivation of the drug into its active metabolite.

“Tests are available to identify a patient’s CYP2C19 genotype. Although these tests are not widely used at this time, some physicians have started to use a strategy of CYP2C19 genotyping among participants initiating treatment with clopidogrel. Moving forward, point-of-care genotyping will likely [become] available, and this technology could further ease the implementation of CYP2C19 testing for interested clinicians and patients,” they added.

This study was funded in part by the National Institutes of Health. Dr. Mega reported ties to Bayer Healthcare, Bristol-Myers Squibb and Sanofi-Aventis (comakers of Plavix), Daiichi Sankyo, Eli Lilly & Co., Johnson & Johnson, Accumetrics Inc., Nanosphere Inc., AstraZeneca, and Novartis. Her associates reported numerous ties to drug and device manufacturers.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events among patients who have RA, according to a report published in the Annals of the Rheumatic Diseases.

Clinicians therefore can target both types of markers to reduce the incidence of CV events, which are the major source of mortality in patients with RA, said Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women’s Hospital, Boston, and his associates.

The investigators examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients: subjects enrolled in CORRONA (Consortium of Rheumatology Researchers of North America), which includes more than 17,000 patients treated by 268 academic and community rheumatologists at 103 medical centers across the United States. Enrollment began in 2002, and patients were followed through 2006.

For this analysis, published online May 5, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack. Cases of heart failure, peripheral artery disease, and CV-related death were excluded from the study.

The study subjects’ mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years.

There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of approximately 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature (at age 50 years or younger) CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity – disease duration greater than 5 years, radiographically evident joint erosions, subcutaneous nodules, prior total joint replacement, a score of 2 or more on the modified Health Assessment Questionnaire, a score of 23 or more on the Clinical Disease Activity Index, and seropositivity for rheumatoid factor – were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 among patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, Dr. Solomon and his colleagues said (Ann. Rheum. Dis. 2010;69:1920-5).

In statistical models that incorporated both types of risk factors plus patient age and sex, the predictive value was comparable to that calculated using the Framingham risk score, they noted.

“These results suggest that strategies to reduce CV risk should focus on a strategy of controlling both traditional CV risk factors as well as controlling RA severity,” the investigators said.

They added that a large clinical trial assessing use of statins for the primary prevention of CV events in RA patients is now under way, with results expected as early as 2011.

There was no specific support for this analysis. CORRONA has received general support in the last 2 years from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

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 Oct. 25 in the Archives of Internal Medicine

© Bonnie Schupp

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, saving about $98 million in [coronary heart disease] care and $13 million in stroke care (but offset by $6 million in additional non-CHD costs contributed by persons who would otherwise have died),” 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.”

However, despite the growing trend of using barbershops in this manner, the effectiveness of barber-based interventions has not been assessed in a randomized trial.

Dr. Victor and his colleagues did so 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. That represents a nearly 20% improvement over the baseline rate of blood pressure control.

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]).

“Thus, the results of this study provide the first evidence for the effectiveness of a barber-based intervention for controlling hypertension in black men,” they added.

Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, said that using barbershops to convey meaningful health messages and conduct health screening appears to work, given that this intervention achieved a nearly 20% improvement in hypertension control compared with baseline, said.

But there is a greater question, he asserted: “Why must we resort to a community-driven approach that abdicates the responsibility to detect disease and institute preemptive care to well-intentioned, appropriately trained, but nonetheless clinically naive health care providers?”

The implication is that providers have collectively failed to provide adequate fundamental health information – a core foundational element in the practice of medicine. Since the study subjects were largely middle-income men with health insurance coverage, “access to care cannot be invoked as an excuse,” Dr. Yancy said.

Given the men’s ready access to conventional health care, it is “remarkable” that they did not have adequate detection and control of their hypertension, he commented.

“This finding is a cause for great concern because it indicates that simply providing better access to health care does not necessarily result in the delivery of better health care,” added Dr. Yancy, who reported (Arch. Intern. Med. 2010 Oct. 25 [doi:10.1001/archinternmed.2010.404]).

The National Heart, Lung, and Blood Institute, 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. Dr. Yancy reported no financial conflicts of interests.

People who smoked two packs of cigarettes or more a day at midlife were more than twice as likely as nonsmokers to develop dementia and dementia subtypes such as Alzheimer’s disease, according to a report published online Oct. 25 in the Archives of Internal Medicine.

© kutay tanir/iStockphoto.com

The association between midlife smoking and dementia 2-3 decades later remained robust after the data were adjusted to account for several confounding factors, including stroke. Therefore, smoking “seems to have some independent effect on vascular dementia, beyond acceleration of cerebrovascular disease,” said Dr. Minna Rusanen of the department of neurology at the University of Eastern Finland, Kuopio, and her associates.

Very few studies have addressed the long-term cerebrovascular consequences of smoking in middle age, and those that have done so had small sample sizes of predominantly white subjects, the investigators noted (Arch. Intern. Med. 2010 [doi:10.1001/archinternmed.2010.393]).

Dr. Rusanen and her colleagues studied the issue using data from a large, multiethnic cohort of more than 33,000 people who were members of the Kaiser Permanente Medical Care Program of Northern California. The study subjects took part in the Multiphasic Health Checkup and were first assessed at enrollment between 1978 and 1985, when they were aged 50-60 years. For the analysis, the medical records of 21,123 people who were still living and in the health plan at follow-up in 1994 were reviewed for dementia diagnoses.

A total of 5,367 people (25%) were diagnosed by neurologists, neuropsychologists, or internists as having dementia, including 1,136 cases of Alzheimer’s disease and 416 cases of vascular dementia.

After researchers adjusted for age, sex and certain cardiovascular risk factors, they found that people who smoked two or more packs per day at midlife were more than twice as likely as nonsmokers to develop dementia (risk-adjusted hazard ratio, 2.14), Alzheimer’s disease (HR, 2.57), or vascular dementia (HR, 2.72) 20-30 years later.

The association between smoking and dementia risk was analyzed separately for people who had stroke, compared with those who did not have stroke, because stroke is a robust predictor of dementia and is highly associated with smoking. Midlife smoking remained a robust independent predictor of dementia and dementia subtypes in that subanalysis, the investigators said. Compared with nonsmokers who had a stroke, those who had smoked two or more packs per day and had a stroke were 1.83 times more likely to develop dementia.

The link between midlife smoking and later dementia also remained robust when the data were adjusted for patient race, ethnicity, and gender. “Based on the present results, we can postulate that the deleterious effects of smoking on risk of dementia seem to be the same for both sexes and across different ethnic groups,” Dr. Rusanen and her associates said.

The study was supported by the National Graduate School of Clinical Investigation, Kuopio University Hospital, the Juho Vainio Foundation, the Maire Taponen Foundation, Kaiser Permanente Community Benefits, Finland’s National Institute for Health and Welfare, and the Academy of Finland. One of Dr. Rusanen’s associates reported ties to Elan Corp., Pfizer, Janssen, and Novartis.

People who smoked two packs of cigarettes or more a day at midlife were more than twice as likely as nonsmokers to develop dementia and dementia subtypes such as Alzheimer’s disease, according to a report published online Oct. 25 in the Archives of Internal Medicine.

© kutay tanir/iStockphoto.com

The association between midlife smoking and dementia 2-3 decades later remained robust after the data were adjusted to account for several confounding factors, including stroke. Therefore, smoking “seems to have some independent effect on vascular dementia, beyond acceleration of cerebrovascular disease,” said Dr. Minna Rusanen of the department of neurology at the University of Eastern Finland, Kuopio, and her associates.

Very few studies have addressed the long-term cerebrovascular consequences of smoking in middle age, and those that have done so had small sample sizes of predominantly white subjects, the investigators noted (Arch. Intern. Med. 2010 [doi:10.1001/archinternmed.2010.393]).

Dr. Rusanen and her colleagues studied the issue using data from a large, multiethnic cohort of more than 33,000 people who were members of the Kaiser Permanente Medical Care Program of Northern California. The study subjects took part in the Multiphasic Health Checkup and were first assessed at enrollment between 1978 and 1985, when they were aged 50-60 years. For the analysis, the medical records of 21,123 people who were still living and in the health plan at follow-up in 1994 were reviewed for dementia diagnoses.

A total of 5,367 people (25%) were diagnosed by neurologists, neuropsychologists, or internists as having dementia, including 1,136 cases of Alzheimer’s disease and 416 cases of vascular dementia.

After researchers adjusted for age, sex and certain cardiovascular risk factors, they found that people who smoked two or more packs per day at midlife were more than twice as likely as nonsmokers to develop dementia (risk-adjusted hazard ratio, 2.14), Alzheimer’s disease (HR, 2.57), or vascular dementia (HR, 2.72) 20-30 years later.

The association between smoking and dementia risk was analyzed separately for people who had stroke, compared with those who did not have stroke, because stroke is a robust predictor of dementia and is highly associated with smoking. Midlife smoking remained a robust independent predictor of dementia and dementia subtypes in that subanalysis, the investigators said. Compared with nonsmokers who had a stroke, those who had smoked two or more packs per day and had a stroke were 1.83 times more likely to develop dementia.

The link between midlife smoking and later dementia also remained robust when the data were adjusted for patient race, ethnicity, and gender. “Based on the present results, we can postulate that the deleterious effects of smoking on risk of dementia seem to be the same for both sexes and across different ethnic groups,” Dr. Rusanen and her associates said.

The study was supported by the National Graduate School of Clinical Investigation, Kuopio University Hospital, the Juho Vainio Foundation, the Maire Taponen Foundation, Kaiser Permanente Community Benefits, Finland’s National Institute for Health and Welfare, and the Academy of Finland. One of Dr. Rusanen’s associates reported ties to Elan Corp., Pfizer, Janssen, and Novartis.

People who smoked two packs of cigarettes or more a day at midlife were more than twice as likely as nonsmokers to develop dementia and dementia subtypes such as Alzheimer’s disease, according to a report published online Oct. 25 in the Archives of Internal Medicine.

© kutay tanir/iStockphoto.com

The association between midlife smoking and dementia 2-3 decades later remained robust after the data were adjusted to account for several confounding factors, including stroke. Therefore, smoking “seems to have some independent effect on vascular dementia, beyond acceleration of cerebrovascular disease,” said Dr. Minna Rusanen of the department of neurology at the University of Eastern Finland, Kuopio, and her associates.

Very few studies have addressed the long-term cerebrovascular consequences of smoking in middle age, and those that have done so had small sample sizes of predominantly white subjects, the investigators noted (Arch. Intern. Med. 2010 [doi:10.1001/archinternmed.2010.393]).

Dr. Rusanen and her colleagues studied the issue using data from a large, multiethnic cohort of more than 33,000 people who were members of the Kaiser Permanente Medical Care Program of Northern California. The study subjects took part in the Multiphasic Health Checkup and were first assessed at enrollment between 1978 and 1985, when they were aged 50-60 years. For the analysis, the medical records of 21,123 people who were still living and in the health plan at follow-up in 1994 were reviewed for dementia diagnoses.

A total of 5,367 people (25%) were diagnosed by neurologists, neuropsychologists, or internists as having dementia, including 1,136 cases of Alzheimer’s disease and 416 cases of vascular dementia.

After researchers adjusted for age, sex and certain cardiovascular risk factors, they found that people who smoked two or more packs per day at midlife were more than twice as likely as nonsmokers to develop dementia (risk-adjusted hazard ratio, 2.14), Alzheimer’s disease (HR, 2.57), or vascular dementia (HR, 2.72) 20-30 years later.

The association between smoking and dementia risk was analyzed separately for people who had stroke, compared with those who did not have stroke, because stroke is a robust predictor of dementia and is highly associated with smoking. Midlife smoking remained a robust independent predictor of dementia and dementia subtypes in that subanalysis, the investigators said. Compared with nonsmokers who had a stroke, those who had smoked two or more packs per day and had a stroke were 1.83 times more likely to develop dementia.

The link between midlife smoking and later dementia also remained robust when the data were adjusted for patient race, ethnicity, and gender. “Based on the present results, we can postulate that the deleterious effects of smoking on risk of dementia seem to be the same for both sexes and across different ethnic groups,” Dr. Rusanen and her associates said.

The study was supported by the National Graduate School of Clinical Investigation, Kuopio University Hospital, the Juho Vainio Foundation, the Maire Taponen Foundation, Kaiser Permanente Community Benefits, Finland’s National Institute for Health and Welfare, and the Academy of Finland. One of Dr. Rusanen’s associates reported ties to Elan Corp., Pfizer, Janssen, and Novartis.