Patrice Wendling

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

Neoadjuvant abiraterone helped clear tumors in one-third of men with localized, high-risk prostate cancer in an ongoing randomized phase II trial, investigators report.

At 6 months, a pathological complete response (pCR) or near pCR was achieved by 34% of men given abiraterone (Zytiga) plus prednisone and leuprolide, compared with 15% of men given leuprolide alone (P = .089). Both groups underwent biopsy and further combination therapy with abiraterone, prednisone, and leuprolide before radical prostatectomy.

The 34% response rate is higher than historic controls and unique in the treatment of prostate cancer, where unlike breast and other cancers, neoadjuvant therapies have not shown a benefit to date, Dr. Mary-Ellen Taplin said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

Abiraterone, a highly selective oral CYP17A1 (17 alpha-hydroxylase/C17,20 lyase complex) inhibitor, was approved last September, for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer previously treated with chemotherapy containing docetaxel (Taxotere).

Dr. Taplin, a medical oncologist at the Dana-Farber Cancer Institute in Boston, said the long-term significance of obtaining a complete response needs to be validated in large, randomized trials, but characterized the response rates as "very impressive given the high-risk features of these patients."

Notably, 71% of the 58 patients had a Gleason score of 8-10, 19% had a prostate-specific antigen (PSA) of more than 20 ng/mL, and all had T3 or T4 disease on prostate exam.

Presscast moderator Dr. Nicholas Vogelzang, cochair of the genitourinary committee for U.S. Oncology and the Southwestern Oncology Group, remarked that "This is one of the first, if not the first study, to show that you can make prostate cancer in the prostate gland itself disappear in a reproducible number of patients.

"This is reminiscent of what we see with rectal cancer when we give chemotherapy and radiation prior to surgery and this is what has now become a standard for breast cancer. Theoretically, at least in the breast cancer literature, when you get a complete disappearance in the primary disease, the outcomes are much better than historically."

When asked whether the current data will push clinicians to use abiraterone off-label in earlier-stage disease, Dr. Taplin said it’s unlikely based on results from a safety trial and the cost of the drug at roughly $7,000/month.

The trial enrolled patients with newly diagnosed intermediate and high-risk prostate cancer with at least three positive biopsies and either a Gleason score of 7 or more, stage T3 disease and a PSA of at least 20 ng/mL or a PSA velocity of more than 2 ng/mL per year. Their median age was 58 years.

The men were randomized to 12 weeks of abiraterone 1,000 mg/day plus prednisone 5 mg/day and leuprolide 22.5 mg or leuprolide 22.5 mg alone. A prostate biopsy was then performed and the men received 12 additional weeks of the triple-combination therapy followed by radical prostatectomy.

A pCR was observed in 10% of the 29 men given all 24 weeks of combination abiraterone and 4% of the 27 men given only 12 weeks of the combination therapy (P = .33), Dr. Taplin said.

A near CR, defined by tumor size of 5 mm or less, was reported in 24% and 11% of patients, respectively.

When asked whether patients with a pCR could forgo surgery, Dr. Taplin said it’s possible, but that it would take a very carefully designed trial to make that leap at this point.

"We’re relatively far from doing this at this point, but these drugs, these new hormonal agents are very powerful and it will definitely be an area of investigation," she said.

The neoadjuvant therapy resulted in low systemic and surgical toxicity. Grade 3 adverse events included elevated AST/ALT in 9% and hypokalemia in 5% of all patients. No grade 4 mineralocorticoid-related adverse events were observed.

"We were able to prove in this study that half the amount of prednisone given in more advanced patients – that is just 5 mg/day – prevented any side effects from abiraterone and may reduce the use of higher doses of steroids in all patients being treated with this drug," Dr. Taplin said.

She noted that a similar trial is being planned that would add the novel androgen-receptor antagonist ARN509 to abiraterone and leuprolide, while a second study is ongoing investigating abiraterone and the experimental hormone drug MDV3100 in this group of patients.

The abstract can be viewed at www.abstract.asco.org and will be formally presented at ASCO on June 2 (Abstract 4521).

In related news, the European National Institute for Health and Clinical Excellence just gave abiraterone the nod for late-stage cancer patients in England and Wales, after initially rejecting the drug for not being cost effective at roughly £3,000 a month.

Cougar Biotechnology sponsored the trial. Dr. Taplin reported consulting or advising for and honoraria and research funding from Johnson & Johnson, which markets abiraterone through Janssen Pharmaceuticals. Her coauthors reported financial relationships with several firms including employment and stock ownership with Johnson & Johnson.

Neoadjuvant abiraterone helped clear tumors in one-third of men with localized, high-risk prostate cancer in an ongoing randomized phase II trial, investigators report.

At 6 months, a pathological complete response (pCR) or near pCR was achieved by 34% of men given abiraterone (Zytiga) plus prednisone and leuprolide, compared with 15% of men given leuprolide alone (P = .089). Both groups underwent biopsy and further combination therapy with abiraterone, prednisone, and leuprolide before radical prostatectomy.

The 34% response rate is higher than historic controls and unique in the treatment of prostate cancer, where unlike breast and other cancers, neoadjuvant therapies have not shown a benefit to date, Dr. Mary-Ellen Taplin said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

Abiraterone, a highly selective oral CYP17A1 (17 alpha-hydroxylase/C17,20 lyase complex) inhibitor, was approved last September, for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer previously treated with chemotherapy containing docetaxel (Taxotere).

Dr. Taplin, a medical oncologist at the Dana-Farber Cancer Institute in Boston, said the long-term significance of obtaining a complete response needs to be validated in large, randomized trials, but characterized the response rates as "very impressive given the high-risk features of these patients."

Notably, 71% of the 58 patients had a Gleason score of 8-10, 19% had a prostate-specific antigen (PSA) of more than 20 ng/mL, and all had T3 or T4 disease on prostate exam.

Presscast moderator Dr. Nicholas Vogelzang, cochair of the genitourinary committee for U.S. Oncology and the Southwestern Oncology Group, remarked that "This is one of the first, if not the first study, to show that you can make prostate cancer in the prostate gland itself disappear in a reproducible number of patients.

"This is reminiscent of what we see with rectal cancer when we give chemotherapy and radiation prior to surgery and this is what has now become a standard for breast cancer. Theoretically, at least in the breast cancer literature, when you get a complete disappearance in the primary disease, the outcomes are much better than historically."

When asked whether the current data will push clinicians to use abiraterone off-label in earlier-stage disease, Dr. Taplin said it’s unlikely based on results from a safety trial and the cost of the drug at roughly $7,000/month.

The trial enrolled patients with newly diagnosed intermediate and high-risk prostate cancer with at least three positive biopsies and either a Gleason score of 7 or more, stage T3 disease and a PSA of at least 20 ng/mL or a PSA velocity of more than 2 ng/mL per year. Their median age was 58 years.

The men were randomized to 12 weeks of abiraterone 1,000 mg/day plus prednisone 5 mg/day and leuprolide 22.5 mg or leuprolide 22.5 mg alone. A prostate biopsy was then performed and the men received 12 additional weeks of the triple-combination therapy followed by radical prostatectomy.

A pCR was observed in 10% of the 29 men given all 24 weeks of combination abiraterone and 4% of the 27 men given only 12 weeks of the combination therapy (P = .33), Dr. Taplin said.

A near CR, defined by tumor size of 5 mm or less, was reported in 24% and 11% of patients, respectively.

When asked whether patients with a pCR could forgo surgery, Dr. Taplin said it’s possible, but that it would take a very carefully designed trial to make that leap at this point.

"We’re relatively far from doing this at this point, but these drugs, these new hormonal agents are very powerful and it will definitely be an area of investigation," she said.

The neoadjuvant therapy resulted in low systemic and surgical toxicity. Grade 3 adverse events included elevated AST/ALT in 9% and hypokalemia in 5% of all patients. No grade 4 mineralocorticoid-related adverse events were observed.

"We were able to prove in this study that half the amount of prednisone given in more advanced patients – that is just 5 mg/day – prevented any side effects from abiraterone and may reduce the use of higher doses of steroids in all patients being treated with this drug," Dr. Taplin said.

She noted that a similar trial is being planned that would add the novel androgen-receptor antagonist ARN509 to abiraterone and leuprolide, while a second study is ongoing investigating abiraterone and the experimental hormone drug MDV3100 in this group of patients.

The abstract can be viewed at www.abstract.asco.org and will be formally presented at ASCO on June 2 (Abstract 4521).

In related news, the European National Institute for Health and Clinical Excellence just gave abiraterone the nod for late-stage cancer patients in England and Wales, after initially rejecting the drug for not being cost effective at roughly £3,000 a month.

Cougar Biotechnology sponsored the trial. Dr. Taplin reported consulting or advising for and honoraria and research funding from Johnson & Johnson, which markets abiraterone through Janssen Pharmaceuticals. Her coauthors reported financial relationships with several firms including employment and stock ownership with Johnson & Johnson.

Neoadjuvant abiraterone helped clear tumors in one-third of men with localized, high-risk prostate cancer in an ongoing randomized phase II trial, investigators report.

At 6 months, a pathological complete response (pCR) or near pCR was achieved by 34% of men given abiraterone (Zytiga) plus prednisone and leuprolide, compared with 15% of men given leuprolide alone (P = .089). Both groups underwent biopsy and further combination therapy with abiraterone, prednisone, and leuprolide before radical prostatectomy.

The 34% response rate is higher than historic controls and unique in the treatment of prostate cancer, where unlike breast and other cancers, neoadjuvant therapies have not shown a benefit to date, Dr. Mary-Ellen Taplin said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

Abiraterone, a highly selective oral CYP17A1 (17 alpha-hydroxylase/C17,20 lyase complex) inhibitor, was approved last September, for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer previously treated with chemotherapy containing docetaxel (Taxotere).

Dr. Taplin, a medical oncologist at the Dana-Farber Cancer Institute in Boston, said the long-term significance of obtaining a complete response needs to be validated in large, randomized trials, but characterized the response rates as "very impressive given the high-risk features of these patients."

Notably, 71% of the 58 patients had a Gleason score of 8-10, 19% had a prostate-specific antigen (PSA) of more than 20 ng/mL, and all had T3 or T4 disease on prostate exam.

Presscast moderator Dr. Nicholas Vogelzang, cochair of the genitourinary committee for U.S. Oncology and the Southwestern Oncology Group, remarked that "This is one of the first, if not the first study, to show that you can make prostate cancer in the prostate gland itself disappear in a reproducible number of patients.

"This is reminiscent of what we see with rectal cancer when we give chemotherapy and radiation prior to surgery and this is what has now become a standard for breast cancer. Theoretically, at least in the breast cancer literature, when you get a complete disappearance in the primary disease, the outcomes are much better than historically."

When asked whether the current data will push clinicians to use abiraterone off-label in earlier-stage disease, Dr. Taplin said it’s unlikely based on results from a safety trial and the cost of the drug at roughly $7,000/month.

The trial enrolled patients with newly diagnosed intermediate and high-risk prostate cancer with at least three positive biopsies and either a Gleason score of 7 or more, stage T3 disease and a PSA of at least 20 ng/mL or a PSA velocity of more than 2 ng/mL per year. Their median age was 58 years.

The men were randomized to 12 weeks of abiraterone 1,000 mg/day plus prednisone 5 mg/day and leuprolide 22.5 mg or leuprolide 22.5 mg alone. A prostate biopsy was then performed and the men received 12 additional weeks of the triple-combination therapy followed by radical prostatectomy.

A pCR was observed in 10% of the 29 men given all 24 weeks of combination abiraterone and 4% of the 27 men given only 12 weeks of the combination therapy (P = .33), Dr. Taplin said.

A near CR, defined by tumor size of 5 mm or less, was reported in 24% and 11% of patients, respectively.

When asked whether patients with a pCR could forgo surgery, Dr. Taplin said it’s possible, but that it would take a very carefully designed trial to make that leap at this point.

"We’re relatively far from doing this at this point, but these drugs, these new hormonal agents are very powerful and it will definitely be an area of investigation," she said.

The neoadjuvant therapy resulted in low systemic and surgical toxicity. Grade 3 adverse events included elevated AST/ALT in 9% and hypokalemia in 5% of all patients. No grade 4 mineralocorticoid-related adverse events were observed.

"We were able to prove in this study that half the amount of prednisone given in more advanced patients – that is just 5 mg/day – prevented any side effects from abiraterone and may reduce the use of higher doses of steroids in all patients being treated with this drug," Dr. Taplin said.

She noted that a similar trial is being planned that would add the novel androgen-receptor antagonist ARN509 to abiraterone and leuprolide, while a second study is ongoing investigating abiraterone and the experimental hormone drug MDV3100 in this group of patients.

The abstract can be viewed at www.abstract.asco.org and will be formally presented at ASCO on June 2 (Abstract 4521).

In related news, the European National Institute for Health and Clinical Excellence just gave abiraterone the nod for late-stage cancer patients in England and Wales, after initially rejecting the drug for not being cost effective at roughly £3,000 a month.

Cougar Biotechnology sponsored the trial. Dr. Taplin reported consulting or advising for and honoraria and research funding from Johnson & Johnson, which markets abiraterone through Janssen Pharmaceuticals. Her coauthors reported financial relationships with several firms including employment and stock ownership with Johnson & Johnson.

DALLAS – In a surprising twist, multidrug resistance and antibiotic appropriateness were not correlated with mortality in a retrospective analysis of critically ill patients infected with Acinetobacter bacillus.

Acinetobacter infections among critically ill patients are increasing and have been associated with mortality rates of 26%-68%. The mortality rates are thought to be driven by high rates of multidrug resistance and subsequent delays in appropriate antimicrobial therapy, Claire Murphy, Pharm.D., explained at the annual meeting of the Surgical Infection Society.

She presented data on 156 surgical and medical ICU patients with at least one positive Acinetobacter culture and associated clinical symptoms who were admitted to an ICU between January 2006 and December 2009. In-hospital mortality was 35%.

Patients who died had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) II scores than did survivors (22.3 vs. 19.5; P = .02), and were more likely to be surgical patients (50% vs. 33.3%; P = .04) and to be in an immunosuppressed state (33.3% vs. 16.7%; P = .02).

Survivors were significantly younger (53 years vs. 59 years; P = .006), and – inexplicably – more likely to have prior colonization or infection with methicillin-resistant Staphylococcus aureus (4% vs. 2%; P = .04), said Dr. Murphy of the department of surgery at the Ohio State University, Columbus.

Respiratory infections were the most common source of Acinetobacter for all patients. Survivors were more likely to have respiratory sources of infection (82.5% vs. 67%; P = .02), whereas nonsurvivors had a higher incidence of Acinetobacter bacteremia, including both secondary and catheter-related bacteremias (43% vs. 8%; P less than .001).

Multidrug resistance rates were similar among survivors and nonsurvivors at 64% and 70.4%, respectively, although there was a slight trend toward increased resistance among nonsurvivors for cefepime (Maxipime), impinem (Primaxin IV/Primaxin IM), and tigecycline (Tygacil), she said.

Rates of appropriate empirical antibiotic coverage were not significantly different, at 18.5% among nonsurvivors and 28.4% among survivors, although survivors were more likely to receive a broad-spectrum carbapenem as empirical therapy (33% vs. 17%; P = .02).

ICU stay, hospital length of stay, and duration of mechanical ventilation were also similar.

Janice Haney Carr/Centers for Disease Control

In a multivariate analysis that was adjusted for potential confounders, the independent predictors of mortality were bacteremia (odds ratio, 14.1; P less than .001), immunosuppression (OR, 2.76; P = .04), and higher severity of illness by APACHE II score (OR, 1.1; P = .002).

The use of the carbapenem antibiotic imipenem as directed therapy was protective (OR, 0.29; P = .012).

"A carbapenem should be considered for [empirical] therapy in ICU patients at risk for Acinetobacter infection," Dr. Murphy said.

Invited discussant Dr. Nicholas Namias, chief of trauma and professor of surgery at the University of Miami Health System, observed that the 35% mortality rate was disturbingly high, but not unexpected. He asked whether the use of carbapenems was forced, in a sense, by the susceptibility pattern of the isolate, and whether patients might have done better if they had been given an antibiotic like colistin.

Dr. Murphy agreed that the choice of carbapenem was directed by susceptibility patterns, and remarked that clinicians tend to lean toward a carbapenem because they’re more comfortable administering and dosing a carbapenem (particularly in complex cases, such as obese patients or those on renal replacement therapy) than colistin.

Dr. Namias also asked how empirical therapy is selected, and how the results might look if only carbapenem-resistant patients were included in the analysis. Dr. Murphy replied that the hospital does not have a fixed rotation, but reviews its ICU-specific antibiograms on an annual basis to determine its standard empirical therapy.

The investigators plan to study outcomes in carbapenem-resistant patients, said Dr. Murphy, but she pointed out that more than half of the patients in the current study were carbapenem resistant. She suggested that a carbapenem may still be beneficial in this setting because there are in vitro data showing synergy between carbapenems and other antibiotics, including colistin, tigecycline, and amikacin. Extended infusions of impinem were not used during the study period, although the hospital recently began using 4-hour infusions of doripenem (Doribax).

The authors reported no relevant conflicts of interest.

DALLAS – In a surprising twist, multidrug resistance and antibiotic appropriateness were not correlated with mortality in a retrospective analysis of critically ill patients infected with Acinetobacter bacillus.

Acinetobacter infections among critically ill patients are increasing and have been associated with mortality rates of 26%-68%. The mortality rates are thought to be driven by high rates of multidrug resistance and subsequent delays in appropriate antimicrobial therapy, Claire Murphy, Pharm.D., explained at the annual meeting of the Surgical Infection Society.

She presented data on 156 surgical and medical ICU patients with at least one positive Acinetobacter culture and associated clinical symptoms who were admitted to an ICU between January 2006 and December 2009. In-hospital mortality was 35%.

Patients who died had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) II scores than did survivors (22.3 vs. 19.5; P = .02), and were more likely to be surgical patients (50% vs. 33.3%; P = .04) and to be in an immunosuppressed state (33.3% vs. 16.7%; P = .02).

Survivors were significantly younger (53 years vs. 59 years; P = .006), and – inexplicably – more likely to have prior colonization or infection with methicillin-resistant Staphylococcus aureus (4% vs. 2%; P = .04), said Dr. Murphy of the department of surgery at the Ohio State University, Columbus.

Respiratory infections were the most common source of Acinetobacter for all patients. Survivors were more likely to have respiratory sources of infection (82.5% vs. 67%; P = .02), whereas nonsurvivors had a higher incidence of Acinetobacter bacteremia, including both secondary and catheter-related bacteremias (43% vs. 8%; P less than .001).

Multidrug resistance rates were similar among survivors and nonsurvivors at 64% and 70.4%, respectively, although there was a slight trend toward increased resistance among nonsurvivors for cefepime (Maxipime), impinem (Primaxin IV/Primaxin IM), and tigecycline (Tygacil), she said.

Rates of appropriate empirical antibiotic coverage were not significantly different, at 18.5% among nonsurvivors and 28.4% among survivors, although survivors were more likely to receive a broad-spectrum carbapenem as empirical therapy (33% vs. 17%; P = .02).

ICU stay, hospital length of stay, and duration of mechanical ventilation were also similar.

Janice Haney Carr/Centers for Disease Control

In a multivariate analysis that was adjusted for potential confounders, the independent predictors of mortality were bacteremia (odds ratio, 14.1; P less than .001), immunosuppression (OR, 2.76; P = .04), and higher severity of illness by APACHE II score (OR, 1.1; P = .002).

The use of the carbapenem antibiotic imipenem as directed therapy was protective (OR, 0.29; P = .012).

"A carbapenem should be considered for [empirical] therapy in ICU patients at risk for Acinetobacter infection," Dr. Murphy said.

Invited discussant Dr. Nicholas Namias, chief of trauma and professor of surgery at the University of Miami Health System, observed that the 35% mortality rate was disturbingly high, but not unexpected. He asked whether the use of carbapenems was forced, in a sense, by the susceptibility pattern of the isolate, and whether patients might have done better if they had been given an antibiotic like colistin.

Dr. Murphy agreed that the choice of carbapenem was directed by susceptibility patterns, and remarked that clinicians tend to lean toward a carbapenem because they’re more comfortable administering and dosing a carbapenem (particularly in complex cases, such as obese patients or those on renal replacement therapy) than colistin.

Dr. Namias also asked how empirical therapy is selected, and how the results might look if only carbapenem-resistant patients were included in the analysis. Dr. Murphy replied that the hospital does not have a fixed rotation, but reviews its ICU-specific antibiograms on an annual basis to determine its standard empirical therapy.

The investigators plan to study outcomes in carbapenem-resistant patients, said Dr. Murphy, but she pointed out that more than half of the patients in the current study were carbapenem resistant. She suggested that a carbapenem may still be beneficial in this setting because there are in vitro data showing synergy between carbapenems and other antibiotics, including colistin, tigecycline, and amikacin. Extended infusions of impinem were not used during the study period, although the hospital recently began using 4-hour infusions of doripenem (Doribax).

The authors reported no relevant conflicts of interest.

DALLAS – In a surprising twist, multidrug resistance and antibiotic appropriateness were not correlated with mortality in a retrospective analysis of critically ill patients infected with Acinetobacter bacillus.

Acinetobacter infections among critically ill patients are increasing and have been associated with mortality rates of 26%-68%. The mortality rates are thought to be driven by high rates of multidrug resistance and subsequent delays in appropriate antimicrobial therapy, Claire Murphy, Pharm.D., explained at the annual meeting of the Surgical Infection Society.

She presented data on 156 surgical and medical ICU patients with at least one positive Acinetobacter culture and associated clinical symptoms who were admitted to an ICU between January 2006 and December 2009. In-hospital mortality was 35%.

Patients who died had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) II scores than did survivors (22.3 vs. 19.5; P = .02), and were more likely to be surgical patients (50% vs. 33.3%; P = .04) and to be in an immunosuppressed state (33.3% vs. 16.7%; P = .02).

Survivors were significantly younger (53 years vs. 59 years; P = .006), and – inexplicably – more likely to have prior colonization or infection with methicillin-resistant Staphylococcus aureus (4% vs. 2%; P = .04), said Dr. Murphy of the department of surgery at the Ohio State University, Columbus.

Respiratory infections were the most common source of Acinetobacter for all patients. Survivors were more likely to have respiratory sources of infection (82.5% vs. 67%; P = .02), whereas nonsurvivors had a higher incidence of Acinetobacter bacteremia, including both secondary and catheter-related bacteremias (43% vs. 8%; P less than .001).

Multidrug resistance rates were similar among survivors and nonsurvivors at 64% and 70.4%, respectively, although there was a slight trend toward increased resistance among nonsurvivors for cefepime (Maxipime), impinem (Primaxin IV/Primaxin IM), and tigecycline (Tygacil), she said.

Rates of appropriate empirical antibiotic coverage were not significantly different, at 18.5% among nonsurvivors and 28.4% among survivors, although survivors were more likely to receive a broad-spectrum carbapenem as empirical therapy (33% vs. 17%; P = .02).

ICU stay, hospital length of stay, and duration of mechanical ventilation were also similar.

Janice Haney Carr/Centers for Disease Control

In a multivariate analysis that was adjusted for potential confounders, the independent predictors of mortality were bacteremia (odds ratio, 14.1; P less than .001), immunosuppression (OR, 2.76; P = .04), and higher severity of illness by APACHE II score (OR, 1.1; P = .002).

The use of the carbapenem antibiotic imipenem as directed therapy was protective (OR, 0.29; P = .012).

"A carbapenem should be considered for [empirical] therapy in ICU patients at risk for Acinetobacter infection," Dr. Murphy said.

Invited discussant Dr. Nicholas Namias, chief of trauma and professor of surgery at the University of Miami Health System, observed that the 35% mortality rate was disturbingly high, but not unexpected. He asked whether the use of carbapenems was forced, in a sense, by the susceptibility pattern of the isolate, and whether patients might have done better if they had been given an antibiotic like colistin.

Dr. Murphy agreed that the choice of carbapenem was directed by susceptibility patterns, and remarked that clinicians tend to lean toward a carbapenem because they’re more comfortable administering and dosing a carbapenem (particularly in complex cases, such as obese patients or those on renal replacement therapy) than colistin.

Dr. Namias also asked how empirical therapy is selected, and how the results might look if only carbapenem-resistant patients were included in the analysis. Dr. Murphy replied that the hospital does not have a fixed rotation, but reviews its ICU-specific antibiograms on an annual basis to determine its standard empirical therapy.

The investigators plan to study outcomes in carbapenem-resistant patients, said Dr. Murphy, but she pointed out that more than half of the patients in the current study were carbapenem resistant. She suggested that a carbapenem may still be beneficial in this setting because there are in vitro data showing synergy between carbapenems and other antibiotics, including colistin, tigecycline, and amikacin. Extended infusions of impinem were not used during the study period, although the hospital recently began using 4-hour infusions of doripenem (Doribax).

The authors reported no relevant conflicts of interest.

DALLAS – Unannounced surveillance detected Acinetobacter contamination in more than one-fourth of burn/trauma intensive care unit rooms tested at a Miami hospital.

Although 58% of rooms housed an Acinetobacter-positive patient, 42% had patients who were negative for the aerobic gram-negative bacillus.

Photo courtesy Janice Haney Carr/CDC

"That’s a worrisome number because those patients are now at risk of picking up Acinetobacter from their environment," senior author Dr. Nicholas Namias said at the annual meeting of the Surgical Infection Society.

Acinetobacter has become one of the preeminent ICU pathogens and is resistant to simple cleaning and many commonly prescribed antibiotics.

New acquisitions of carbapenem-resistant Acinetobacter at the University of Miami’s Jackson Memorial Hospital, where the study was conducted, were high in early 2011 at up to 13/week, but leveled off to zero in some weeks after a bundle intervention was put in place. The bundle included grouping a positive patient cohort, active surveillance of patients using rectal swab cultures, hand hygiene education, operating room interventions, and weekly environmental cleaning feedback.

The 25-bed ICU was cultured weekly and the cultures subjected to pulsed field gel electrophoresis. Ultraviolet powder, invisible to the naked eye, was also placed on surfaces throughout the ICU and checked 48 hours later with ultraviolet light to see if they were cleaned.

Patrice Wendling/IMNG Medical Media

"We even went so far as to place plates on high surfaces where nobody reaches to see if Acinetobacter could grow out of thin air," said Dr. Namias, chief of trauma and professor of surgery at the University of Miami Health System.

Of the 213 rooms cultured over 15 weeks, 57 (27%) were positive for Acinetobacter. More than 90% of samples were identified as Acinetobacter baumannii. Contaminated sites included 38 bed rails (67%), 21 intravenous pumps (37%), 6 bedside tables (11%), and 3 ventilator control panels (5%).

"This actually turned out to be a major issue, because once you discover they’re dirty, it becomes a big question of who’s supposed to clean them," he said. "Understandably, environmental staff was kind of hesitant to touch IV pumps and ventilator control panels, and the nurses are probably overtrained to be cleaning bed rails and bedside tables. So you end up having to use techs, the people who go around doing urimeters and finger-prick glucose, but you have to make sure they’re trained in proper hand hygiene."

At baseline, only slightly more than 40% of surfaces had been cleaned at 48 hours – a percentage that Dr. Namias described as alarming, but typical in surveillance studies. Once the ultraviolet "spying" began, and environmental services was told that surfaces were unclean, there was a very quick response. Within 1 week, the percentage of surfaces cleaned at 48 hours rose to nearly 100%, where it has remained.

"Once they know they are being watched, you can have them do the right thing," he said.

In a separate analysis, similar results were achieved in the operating room, where the percentage of surfaces cleaned at 48 hours increased from 47% to 82% after the educational and cleaning intervention.

Importantly, the number of new acquisitions of Acinetobacter decreased concomitantly from 1.40 patients/week to 0.37; and from 9.2/month during the first 6 months of 2011 to 3.3/month during the last 6 months (P = .003).

Invited discussant Dr. Heather Evans, a trauma and acute care surgeon and surgical intensivist with the University of Washington in Seattle, thanked the program committee for selecting the abstract for oral discussion, citing the relevance of infection-control data to the practicing clinician and to prevention efforts. She went on to ask whether the hospital regularly uses active surveillance for Acinetobacter and contact precautions when a patient is colonized and whether the hospital would presumptively put a patient on contact precautions if they reach a certain level.

Dr. Evans also asked whether cleaning personnel can game the system, citing a recent paper by lead study author Dr. L. Silvia Munoz-Price that identified preferential cleaning of white UV powder targets among units with high levels of experience with UV powder (Infect. Control Hosp. Epidemiol. 2012;33:92-5). Dr. Namias said it’s entirely possible that personnel are gaming the system, but noted that Acinetobacter is also airborne.

Finally, an audience member remarked that the open-air design of the trauma ICU, as shown in an illustration, may be contributing to the unusually high rates of contamination. Dr. Namias agreed that the unit is due for an update and said it was designed before it was known that closed units are best.

Dr. Munoz-Price, medical director of infection control at Jackson Memorial, said they are currently performing multivariable analyses to better understand the factors associated with higher environmental contamination.

"The control of Acinetobacter within a hospital setting deals with the interaction of patient’s bioburden, health care worker hands/uniforms, and contaminated objects in the environment," she said in an interview. "This cycle of contamination needs to be tackled at different levels in order to sustain good outcomes."

The authors reported no relevant conflicts of interest.

DALLAS – Unannounced surveillance detected Acinetobacter contamination in more than one-fourth of burn/trauma intensive care unit rooms tested at a Miami hospital.

Although 58% of rooms housed an Acinetobacter-positive patient, 42% had patients who were negative for the aerobic gram-negative bacillus.

Photo courtesy Janice Haney Carr/CDC

"That’s a worrisome number because those patients are now at risk of picking up Acinetobacter from their environment," senior author Dr. Nicholas Namias said at the annual meeting of the Surgical Infection Society.

Acinetobacter has become one of the preeminent ICU pathogens and is resistant to simple cleaning and many commonly prescribed antibiotics.

New acquisitions of carbapenem-resistant Acinetobacter at the University of Miami’s Jackson Memorial Hospital, where the study was conducted, were high in early 2011 at up to 13/week, but leveled off to zero in some weeks after a bundle intervention was put in place. The bundle included grouping a positive patient cohort, active surveillance of patients using rectal swab cultures, hand hygiene education, operating room interventions, and weekly environmental cleaning feedback.

The 25-bed ICU was cultured weekly and the cultures subjected to pulsed field gel electrophoresis. Ultraviolet powder, invisible to the naked eye, was also placed on surfaces throughout the ICU and checked 48 hours later with ultraviolet light to see if they were cleaned.

Patrice Wendling/IMNG Medical Media

"We even went so far as to place plates on high surfaces where nobody reaches to see if Acinetobacter could grow out of thin air," said Dr. Namias, chief of trauma and professor of surgery at the University of Miami Health System.

Of the 213 rooms cultured over 15 weeks, 57 (27%) were positive for Acinetobacter. More than 90% of samples were identified as Acinetobacter baumannii. Contaminated sites included 38 bed rails (67%), 21 intravenous pumps (37%), 6 bedside tables (11%), and 3 ventilator control panels (5%).

"This actually turned out to be a major issue, because once you discover they’re dirty, it becomes a big question of who’s supposed to clean them," he said. "Understandably, environmental staff was kind of hesitant to touch IV pumps and ventilator control panels, and the nurses are probably overtrained to be cleaning bed rails and bedside tables. So you end up having to use techs, the people who go around doing urimeters and finger-prick glucose, but you have to make sure they’re trained in proper hand hygiene."

At baseline, only slightly more than 40% of surfaces had been cleaned at 48 hours – a percentage that Dr. Namias described as alarming, but typical in surveillance studies. Once the ultraviolet "spying" began, and environmental services was told that surfaces were unclean, there was a very quick response. Within 1 week, the percentage of surfaces cleaned at 48 hours rose to nearly 100%, where it has remained.

"Once they know they are being watched, you can have them do the right thing," he said.

In a separate analysis, similar results were achieved in the operating room, where the percentage of surfaces cleaned at 48 hours increased from 47% to 82% after the educational and cleaning intervention.

Importantly, the number of new acquisitions of Acinetobacter decreased concomitantly from 1.40 patients/week to 0.37; and from 9.2/month during the first 6 months of 2011 to 3.3/month during the last 6 months (P = .003).

Invited discussant Dr. Heather Evans, a trauma and acute care surgeon and surgical intensivist with the University of Washington in Seattle, thanked the program committee for selecting the abstract for oral discussion, citing the relevance of infection-control data to the practicing clinician and to prevention efforts. She went on to ask whether the hospital regularly uses active surveillance for Acinetobacter and contact precautions when a patient is colonized and whether the hospital would presumptively put a patient on contact precautions if they reach a certain level.

Dr. Evans also asked whether cleaning personnel can game the system, citing a recent paper by lead study author Dr. L. Silvia Munoz-Price that identified preferential cleaning of white UV powder targets among units with high levels of experience with UV powder (Infect. Control Hosp. Epidemiol. 2012;33:92-5). Dr. Namias said it’s entirely possible that personnel are gaming the system, but noted that Acinetobacter is also airborne.

Finally, an audience member remarked that the open-air design of the trauma ICU, as shown in an illustration, may be contributing to the unusually high rates of contamination. Dr. Namias agreed that the unit is due for an update and said it was designed before it was known that closed units are best.

Dr. Munoz-Price, medical director of infection control at Jackson Memorial, said they are currently performing multivariable analyses to better understand the factors associated with higher environmental contamination.

"The control of Acinetobacter within a hospital setting deals with the interaction of patient’s bioburden, health care worker hands/uniforms, and contaminated objects in the environment," she said in an interview. "This cycle of contamination needs to be tackled at different levels in order to sustain good outcomes."

The authors reported no relevant conflicts of interest.

DALLAS – Unannounced surveillance detected Acinetobacter contamination in more than one-fourth of burn/trauma intensive care unit rooms tested at a Miami hospital.

Although 58% of rooms housed an Acinetobacter-positive patient, 42% had patients who were negative for the aerobic gram-negative bacillus.

Photo courtesy Janice Haney Carr/CDC

"That’s a worrisome number because those patients are now at risk of picking up Acinetobacter from their environment," senior author Dr. Nicholas Namias said at the annual meeting of the Surgical Infection Society.

Acinetobacter has become one of the preeminent ICU pathogens and is resistant to simple cleaning and many commonly prescribed antibiotics.

New acquisitions of carbapenem-resistant Acinetobacter at the University of Miami’s Jackson Memorial Hospital, where the study was conducted, were high in early 2011 at up to 13/week, but leveled off to zero in some weeks after a bundle intervention was put in place. The bundle included grouping a positive patient cohort, active surveillance of patients using rectal swab cultures, hand hygiene education, operating room interventions, and weekly environmental cleaning feedback.

The 25-bed ICU was cultured weekly and the cultures subjected to pulsed field gel electrophoresis. Ultraviolet powder, invisible to the naked eye, was also placed on surfaces throughout the ICU and checked 48 hours later with ultraviolet light to see if they were cleaned.

Patrice Wendling/IMNG Medical Media

"We even went so far as to place plates on high surfaces where nobody reaches to see if Acinetobacter could grow out of thin air," said Dr. Namias, chief of trauma and professor of surgery at the University of Miami Health System.

Of the 213 rooms cultured over 15 weeks, 57 (27%) were positive for Acinetobacter. More than 90% of samples were identified as Acinetobacter baumannii. Contaminated sites included 38 bed rails (67%), 21 intravenous pumps (37%), 6 bedside tables (11%), and 3 ventilator control panels (5%).

"This actually turned out to be a major issue, because once you discover they’re dirty, it becomes a big question of who’s supposed to clean them," he said. "Understandably, environmental staff was kind of hesitant to touch IV pumps and ventilator control panels, and the nurses are probably overtrained to be cleaning bed rails and bedside tables. So you end up having to use techs, the people who go around doing urimeters and finger-prick glucose, but you have to make sure they’re trained in proper hand hygiene."

At baseline, only slightly more than 40% of surfaces had been cleaned at 48 hours – a percentage that Dr. Namias described as alarming, but typical in surveillance studies. Once the ultraviolet "spying" began, and environmental services was told that surfaces were unclean, there was a very quick response. Within 1 week, the percentage of surfaces cleaned at 48 hours rose to nearly 100%, where it has remained.

"Once they know they are being watched, you can have them do the right thing," he said.

In a separate analysis, similar results were achieved in the operating room, where the percentage of surfaces cleaned at 48 hours increased from 47% to 82% after the educational and cleaning intervention.

Importantly, the number of new acquisitions of Acinetobacter decreased concomitantly from 1.40 patients/week to 0.37; and from 9.2/month during the first 6 months of 2011 to 3.3/month during the last 6 months (P = .003).

Invited discussant Dr. Heather Evans, a trauma and acute care surgeon and surgical intensivist with the University of Washington in Seattle, thanked the program committee for selecting the abstract for oral discussion, citing the relevance of infection-control data to the practicing clinician and to prevention efforts. She went on to ask whether the hospital regularly uses active surveillance for Acinetobacter and contact precautions when a patient is colonized and whether the hospital would presumptively put a patient on contact precautions if they reach a certain level.

Dr. Evans also asked whether cleaning personnel can game the system, citing a recent paper by lead study author Dr. L. Silvia Munoz-Price that identified preferential cleaning of white UV powder targets among units with high levels of experience with UV powder (Infect. Control Hosp. Epidemiol. 2012;33:92-5). Dr. Namias said it’s entirely possible that personnel are gaming the system, but noted that Acinetobacter is also airborne.

Finally, an audience member remarked that the open-air design of the trauma ICU, as shown in an illustration, may be contributing to the unusually high rates of contamination. Dr. Namias agreed that the unit is due for an update and said it was designed before it was known that closed units are best.

Dr. Munoz-Price, medical director of infection control at Jackson Memorial, said they are currently performing multivariable analyses to better understand the factors associated with higher environmental contamination.

"The control of Acinetobacter within a hospital setting deals with the interaction of patient’s bioburden, health care worker hands/uniforms, and contaminated objects in the environment," she said in an interview. "This cycle of contamination needs to be tackled at different levels in order to sustain good outcomes."

The authors reported no relevant conflicts of interest.

CHICAGO – Coronary dissection, a rare and sometimes fatal condition, surpassed atherosclerosis as the most common cause of pregnancy-associated acute myocardial infarction in a retrospective analysis of 150 women.

Pregnant women also appear to be at increased risk of coronary dissection during coronary angiography and percutaneous coronary intervention, leading to death in one patient, coronary artery bypass grafting in four, and multiple stenting in two.

Patrice Wendling/IMNG Medical Media

Moreover, standard treatment with thrombolytic agents may actually increase the risk of hemorrhage and further progression of the dissection in pregnant patients, Dr. Uri Elkayam explained at the annual meeting of the American College of Cardiology.

"Because of this, we are ready now to come up with some strong recommendations that we hope will be reflected in the guidelines that the approach to heart attack in pregnancy should be different than that recommended in the general population," said Dr. Elkayam, professor of medicine in the cardiovascular medicine division at the University of Southern California in Los Angeles and director of the Heart Failure Program at USC Medical Center and University Hospital.

Although the European Society of Cardiology recently published guidelines for the management of cardiovascular diseases during pregnancy (Eur. Heart J. 2011;32:3147-97), neither the American College of Cardiology nor the American Heart Association has specific guidelines.

The analysis included 150 cases of myocardial infarction during pregnancy or the 12 weeks after delivery that were identified in the literature, consulted on, or cared for by the research team since 2005. The women’s average age was 34 years, and 75% were at least 30 years old.

The cause of acute MI was coronary dissection in 56 of the 129 women who had angiography, with 10 dissections occurring in the third trimester and 41 postpartum. Atherosclerotic coronary artery disease, the most common cause of acute MI in the general population, was identified in only 35 women, followed by intracoronary thrombus without evidence of atherosclerosis in 22, normal coronary anatomy with possible spasm in 16, documented spasm in 3, and takotsubo cardiomyopathy in 1. Four of the 22 patients with intracoronary thrombus did not undergo an angiogram.

Coronary dissection, which is thought to occur during pregnancy because of hormonally mediated weakening of the walls of coronary arteries, was managed with bypass surgery in 41.5% of patients, stenting in 38%, medication without coronary intervention in 22%, and a Bentall procedure in 1%.

Percutaneous coronary intervention (PCI) was performed in 40% of all patients and coronary angiography in 79%.

The use of thrombolytic therapy is relatively contraindicated in pregnancy due to the risk of bleeding. In addition, thrombolytic therapy may not be effective in women with normal coronaries, spasm, or coronary dissection, and in the last group it can even be detrimental, Dr. Elkayam observed.

"Thrombolytic therapy should therefore be considered second choice to primary PCI in patients with ST-segment elevation MI during pregnancy, especially during the third trimester, [in] the peripartum and early postpartum periods when the incidence of dissection is high," he suggested.

The use of angiography to determine the cause of the MI and guide therapy is recommended in pregnant women with ST-segment elevation MI and in other high-risk MI patients, but because of the increased risk of iatrogenic coronary dissection, stable and low-risk non-STEMI patients should be treated noninvasively during pregnancy and postpartum, Dr. Elkayam recommended.

Most women in the current analysis did not present with traditional cardiovascular risk factors. Only 9% had diabetes, 15% had hypertension, and 20% had hyperlipidemia, although one-fourth were smokers.

Maternal mortality was 7%, down from 20% during 1922-1995 and 11% during 1996-2005, as previously reported by the researchers (Ann. Intern. Med. 1996;125:751-62; J. Am. Coll. Cardiol. 2008;52:171-80). In spite of the decreased rate of maternal death, women who experience a pregnancy-related MI are three to five times more likely to die than nonpregnant women of comparable age, he said.

Fetal deaths, driven largely by maternal mortality, were also lower at 5%, compared with 12% and 9% in the previous analyses.

Still, Dr. Elkayam stressed that women should not avoid becoming pregnant because of fears of an MI, as the incidence is extremely low, at one in 16,000 deliveries. Although maternal and fetal mortality have been decreasing, the number of women with cardiac problems in pregnancy is rising due to older maternal age at first pregnancy; a spike in age-related cardiovascular risk factors such as diabetes, obesity, and hypertension; and mostly, improved treatment of congenital heart disease, allowing more women to reach childbearing age.

"In general, most patients with mild and even moderate cardiac problems can become pregnant and have children safely," he said in an interview. "Patients are often getting information that is not realistic, usually exaggerating the risk. The reality is such that most physicians are not interested in really managing this problem, and so oftentimes women with heart disease will get advice not to become pregnant."

Dr. Elkayam said women with heart disease should be treated by a cardiologist and obstetrician experienced in managing cardiac problems in pregnancy, and that high-risk patients should managed by an expert multidisciplinary team in a specialist center. He also called for a national registry, similar to the registry established in Europe, to better track outcomes of pregnancy-related heart disease in general, including MI.

Dr. Elkayam reported no conflicts of interest.

CHICAGO – Coronary dissection, a rare and sometimes fatal condition, surpassed atherosclerosis as the most common cause of pregnancy-associated acute myocardial infarction in a retrospective analysis of 150 women.

Pregnant women also appear to be at increased risk of coronary dissection during coronary angiography and percutaneous coronary intervention, leading to death in one patient, coronary artery bypass grafting in four, and multiple stenting in two.

Patrice Wendling/IMNG Medical Media

Moreover, standard treatment with thrombolytic agents may actually increase the risk of hemorrhage and further progression of the dissection in pregnant patients, Dr. Uri Elkayam explained at the annual meeting of the American College of Cardiology.

"Because of this, we are ready now to come up with some strong recommendations that we hope will be reflected in the guidelines that the approach to heart attack in pregnancy should be different than that recommended in the general population," said Dr. Elkayam, professor of medicine in the cardiovascular medicine division at the University of Southern California in Los Angeles and director of the Heart Failure Program at USC Medical Center and University Hospital.

Although the European Society of Cardiology recently published guidelines for the management of cardiovascular diseases during pregnancy (Eur. Heart J. 2011;32:3147-97), neither the American College of Cardiology nor the American Heart Association has specific guidelines.

The analysis included 150 cases of myocardial infarction during pregnancy or the 12 weeks after delivery that were identified in the literature, consulted on, or cared for by the research team since 2005. The women’s average age was 34 years, and 75% were at least 30 years old.

The cause of acute MI was coronary dissection in 56 of the 129 women who had angiography, with 10 dissections occurring in the third trimester and 41 postpartum. Atherosclerotic coronary artery disease, the most common cause of acute MI in the general population, was identified in only 35 women, followed by intracoronary thrombus without evidence of atherosclerosis in 22, normal coronary anatomy with possible spasm in 16, documented spasm in 3, and takotsubo cardiomyopathy in 1. Four of the 22 patients with intracoronary thrombus did not undergo an angiogram.

Coronary dissection, which is thought to occur during pregnancy because of hormonally mediated weakening of the walls of coronary arteries, was managed with bypass surgery in 41.5% of patients, stenting in 38%, medication without coronary intervention in 22%, and a Bentall procedure in 1%.

Percutaneous coronary intervention (PCI) was performed in 40% of all patients and coronary angiography in 79%.

The use of thrombolytic therapy is relatively contraindicated in pregnancy due to the risk of bleeding. In addition, thrombolytic therapy may not be effective in women with normal coronaries, spasm, or coronary dissection, and in the last group it can even be detrimental, Dr. Elkayam observed.

"Thrombolytic therapy should therefore be considered second choice to primary PCI in patients with ST-segment elevation MI during pregnancy, especially during the third trimester, [in] the peripartum and early postpartum periods when the incidence of dissection is high," he suggested.

The use of angiography to determine the cause of the MI and guide therapy is recommended in pregnant women with ST-segment elevation MI and in other high-risk MI patients, but because of the increased risk of iatrogenic coronary dissection, stable and low-risk non-STEMI patients should be treated noninvasively during pregnancy and postpartum, Dr. Elkayam recommended.

Most women in the current analysis did not present with traditional cardiovascular risk factors. Only 9% had diabetes, 15% had hypertension, and 20% had hyperlipidemia, although one-fourth were smokers.

Maternal mortality was 7%, down from 20% during 1922-1995 and 11% during 1996-2005, as previously reported by the researchers (Ann. Intern. Med. 1996;125:751-62; J. Am. Coll. Cardiol. 2008;52:171-80). In spite of the decreased rate of maternal death, women who experience a pregnancy-related MI are three to five times more likely to die than nonpregnant women of comparable age, he said.

Fetal deaths, driven largely by maternal mortality, were also lower at 5%, compared with 12% and 9% in the previous analyses.

Still, Dr. Elkayam stressed that women should not avoid becoming pregnant because of fears of an MI, as the incidence is extremely low, at one in 16,000 deliveries. Although maternal and fetal mortality have been decreasing, the number of women with cardiac problems in pregnancy is rising due to older maternal age at first pregnancy; a spike in age-related cardiovascular risk factors such as diabetes, obesity, and hypertension; and mostly, improved treatment of congenital heart disease, allowing more women to reach childbearing age.

"In general, most patients with mild and even moderate cardiac problems can become pregnant and have children safely," he said in an interview. "Patients are often getting information that is not realistic, usually exaggerating the risk. The reality is such that most physicians are not interested in really managing this problem, and so oftentimes women with heart disease will get advice not to become pregnant."

Dr. Elkayam said women with heart disease should be treated by a cardiologist and obstetrician experienced in managing cardiac problems in pregnancy, and that high-risk patients should managed by an expert multidisciplinary team in a specialist center. He also called for a national registry, similar to the registry established in Europe, to better track outcomes of pregnancy-related heart disease in general, including MI.

Dr. Elkayam reported no conflicts of interest.

CHICAGO – Coronary dissection, a rare and sometimes fatal condition, surpassed atherosclerosis as the most common cause of pregnancy-associated acute myocardial infarction in a retrospective analysis of 150 women.

Pregnant women also appear to be at increased risk of coronary dissection during coronary angiography and percutaneous coronary intervention, leading to death in one patient, coronary artery bypass grafting in four, and multiple stenting in two.

Patrice Wendling/IMNG Medical Media

Moreover, standard treatment with thrombolytic agents may actually increase the risk of hemorrhage and further progression of the dissection in pregnant patients, Dr. Uri Elkayam explained at the annual meeting of the American College of Cardiology.

"Because of this, we are ready now to come up with some strong recommendations that we hope will be reflected in the guidelines that the approach to heart attack in pregnancy should be different than that recommended in the general population," said Dr. Elkayam, professor of medicine in the cardiovascular medicine division at the University of Southern California in Los Angeles and director of the Heart Failure Program at USC Medical Center and University Hospital.

Although the European Society of Cardiology recently published guidelines for the management of cardiovascular diseases during pregnancy (Eur. Heart J. 2011;32:3147-97), neither the American College of Cardiology nor the American Heart Association has specific guidelines.

The analysis included 150 cases of myocardial infarction during pregnancy or the 12 weeks after delivery that were identified in the literature, consulted on, or cared for by the research team since 2005. The women’s average age was 34 years, and 75% were at least 30 years old.

The cause of acute MI was coronary dissection in 56 of the 129 women who had angiography, with 10 dissections occurring in the third trimester and 41 postpartum. Atherosclerotic coronary artery disease, the most common cause of acute MI in the general population, was identified in only 35 women, followed by intracoronary thrombus without evidence of atherosclerosis in 22, normal coronary anatomy with possible spasm in 16, documented spasm in 3, and takotsubo cardiomyopathy in 1. Four of the 22 patients with intracoronary thrombus did not undergo an angiogram.

Coronary dissection, which is thought to occur during pregnancy because of hormonally mediated weakening of the walls of coronary arteries, was managed with bypass surgery in 41.5% of patients, stenting in 38%, medication without coronary intervention in 22%, and a Bentall procedure in 1%.

Percutaneous coronary intervention (PCI) was performed in 40% of all patients and coronary angiography in 79%.

The use of thrombolytic therapy is relatively contraindicated in pregnancy due to the risk of bleeding. In addition, thrombolytic therapy may not be effective in women with normal coronaries, spasm, or coronary dissection, and in the last group it can even be detrimental, Dr. Elkayam observed.

"Thrombolytic therapy should therefore be considered second choice to primary PCI in patients with ST-segment elevation MI during pregnancy, especially during the third trimester, [in] the peripartum and early postpartum periods when the incidence of dissection is high," he suggested.

The use of angiography to determine the cause of the MI and guide therapy is recommended in pregnant women with ST-segment elevation MI and in other high-risk MI patients, but because of the increased risk of iatrogenic coronary dissection, stable and low-risk non-STEMI patients should be treated noninvasively during pregnancy and postpartum, Dr. Elkayam recommended.

Most women in the current analysis did not present with traditional cardiovascular risk factors. Only 9% had diabetes, 15% had hypertension, and 20% had hyperlipidemia, although one-fourth were smokers.

Maternal mortality was 7%, down from 20% during 1922-1995 and 11% during 1996-2005, as previously reported by the researchers (Ann. Intern. Med. 1996;125:751-62; J. Am. Coll. Cardiol. 2008;52:171-80). In spite of the decreased rate of maternal death, women who experience a pregnancy-related MI are three to five times more likely to die than nonpregnant women of comparable age, he said.

Fetal deaths, driven largely by maternal mortality, were also lower at 5%, compared with 12% and 9% in the previous analyses.

Still, Dr. Elkayam stressed that women should not avoid becoming pregnant because of fears of an MI, as the incidence is extremely low, at one in 16,000 deliveries. Although maternal and fetal mortality have been decreasing, the number of women with cardiac problems in pregnancy is rising due to older maternal age at first pregnancy; a spike in age-related cardiovascular risk factors such as diabetes, obesity, and hypertension; and mostly, improved treatment of congenital heart disease, allowing more women to reach childbearing age.

"In general, most patients with mild and even moderate cardiac problems can become pregnant and have children safely," he said in an interview. "Patients are often getting information that is not realistic, usually exaggerating the risk. The reality is such that most physicians are not interested in really managing this problem, and so oftentimes women with heart disease will get advice not to become pregnant."

Dr. Elkayam said women with heart disease should be treated by a cardiologist and obstetrician experienced in managing cardiac problems in pregnancy, and that high-risk patients should managed by an expert multidisciplinary team in a specialist center. He also called for a national registry, similar to the registry established in Europe, to better track outcomes of pregnancy-related heart disease in general, including MI.

Dr. Elkayam reported no conflicts of interest.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

DALLAS – Clinicians frequently perform bronchoalveolar lavage in ventilated trauma patients without radiologic evidence of pneumonia, according to a retrospective analysis.

Among 1,343 chest x-ray reports from 344 patients who all underwent bronchoalveolar lavage (BAL), there was no mention of infiltrates in 11% and no suspicion of pneumonia in 64%, according to a review that used natural language processing to sift through the reports.

"Our indication for BAL includes chest x-ray infiltrates or a change in chest x-rays, so I was very surprised to see that there were so many BALs done without an infiltrate mentioned in the chest x-ray report," said lead author Dr. Heather L. Evans, a trauma and acute care surgeon and surgical intensivist at the University of Washington in Seattle. "I think that this may be something of a soft call when providers are concerned that the patient has increasing secretions, increasing oxygenation, and worsening sepsis of unknown etiology. Perhaps the chest x-ray is not as firm and fast a rule as we are led to believe."

Indeed, the Centers for Disease Control and Prevention removed the chest x-ray from its new surveillance definition for what is now termed adult ventilator-associated events. The new definition, expected to be implemented in 2013, is not intended for clinical management, leaving physicians in a quandary when making a clinical diagnosis of VAP. Enter natural language processing, a tool that is increasingly being applied in radiology as part of machine learning to aid in-text analysis of radiology reports (Med. Image Anal. 2012 [doi:10.1016/j.media.2012.02.005]).

The investigators used natural language processing coding methods to code 1,343 chest x-ray reports from the day prior, day of, and day after BAL among 344 trauma patients ventilated for more than 48 hours at a level 1 trauma center. Two specially trained reviewers coded the reports using the chest x-ray element from the Clinical Pulmonary Infection Score (CPIS) as "no infiltrate," "diffuse infiltrate or atelectasis," or "focal infiltrate" and scored the reports on a three-point scale for suspicion of pneumonia as "no suspicion," "suspicion," or "probable pneumonia."

The CPIS classifier had a 90% overall accuracy, 93% specificity, 86% sensitivity, and 85% positive predictive value. The suspicion classifier achieved comparable results of 85%, 89%, 78%, and 78%, respectively.

As expected, localized infiltrate was significantly more common in reports from BAL-positive than BAL-negative patients (13% vs. 9%), while no infiltrate was significantly more common in those from BAL-negative patients (15.3% vs. 11.5%). However, 1,013 chest x-ray reports, or 75.4% of the data, fell in-between with diffuse infiltrate or atelectasis and had a 50-50 chance of being diagnosed as VAP, Dr. Evans said at the annual meeting of the Surgical Infection Society.

"Failure to discriminate diffuse infiltrate defines the group where culture data is most useful," she observed.

Radiology reports noting any suspicion of pneumonia were significantly more common in positive-BAL than in negative-BAL patients (45.6% vs. 28%), while reports with no suspicion of pneumonia were significantly more common in BAL-negative patients (68% vs. 60%).

Still, 430 (50%) of the 856 chest x-ray reports with no suspicion of VAP were in patients with BAL-positive results, Dr. Evans pointed out.

To sort out the implications of this finding, the investigators stratified the CPIS data by time and discovered that differences between the BAL-positive and -negative groups regarding the presence or absence of infiltrates were statistically significant only on chest x-ray reports from the day after BAL (P = .004).

"Considering the timing of this chest x-ray report information is absolutely crucial and something we will definitely incorporate in the future," she said, adding that future work will involve evaluation of coded chest x-ray report content in VAP risk assessment.

Invited discussant Dr. Addison K. May, chief of trauma and surgical critical care at Vanderbilt University in Nashville, Tenn., questioned whether the authors were surprised by the findings given that chest x-ray readings and BAL results correlate only about 40% of the time, and asked why the authors chose to include the radiology report from the day after BAL. Dr. Evans said the lack of correlation wasn’t surprising and that chest x-ray report language will be incorporated, along with other available clinical values, into their VAP risk assessment model.

"To exclude the chest x-ray information is to ignore a fundamental piece of diagnostic data that clinicians use all the time," she added. "As much as we don’t like to rely on the chest x-ray, I’m currently doing a qualitative study of the diagnosis of ventilator-associated pneumonia at my institution, and I can tell you in the 15 interviews I’ve done, every single person says the chest x-ray is a fundamental piece that they rely on to make the diagnosis.

"So I think if we’re going to remove the chest x-ray from our definition, whether it’s from surveillance or from the definition that we use clinically, we have to have data to support that it shouldn’t be there."

Dr. Evans said the chest x-ray report from the day after BAL was included to help train the classifier to be accurate, and that the finding of statistical significance only for that day’s chest x-ray report data was unexpected and provocative.

Dr. Pamela Lipsett, immediate past president of the Surgical Infection Society, was involved in the CDC’s redefinition of what is now termed ventilator-associated events. She argued against the use of chest x-rays for VAP diagnosis and said they were removed from the CDC definition because they are unreliable.

Some attendees questioned why the authors didn’t just use a structured method for reading the radiographs. Dr. E. Patchen Dellinger, also a past president of the Society, simply asked, "Haven’t you just proved that we don’t know how to diagnosis VAP and that we should stop taking chest x-rays unless we’re worried about a pneumothorax?"

Dr. Evans replied that there are many other indications for chest x-ray in the ICU, but added that "the days of getting a chest x-ray every morning just because the patient is ventilated are a gross overuse of that imaging modality."

The authors reported no relevant conflicts of interest.

DALLAS – Clinicians frequently perform bronchoalveolar lavage in ventilated trauma patients without radiologic evidence of pneumonia, according to a retrospective analysis.

Among 1,343 chest x-ray reports from 344 patients who all underwent bronchoalveolar lavage (BAL), there was no mention of infiltrates in 11% and no suspicion of pneumonia in 64%, according to a review that used natural language processing to sift through the reports.

"Our indication for BAL includes chest x-ray infiltrates or a change in chest x-rays, so I was very surprised to see that there were so many BALs done without an infiltrate mentioned in the chest x-ray report," said lead author Dr. Heather L. Evans, a trauma and acute care surgeon and surgical intensivist at the University of Washington in Seattle. "I think that this may be something of a soft call when providers are concerned that the patient has increasing secretions, increasing oxygenation, and worsening sepsis of unknown etiology. Perhaps the chest x-ray is not as firm and fast a rule as we are led to believe."

Indeed, the Centers for Disease Control and Prevention removed the chest x-ray from its new surveillance definition for what is now termed adult ventilator-associated events. The new definition, expected to be implemented in 2013, is not intended for clinical management, leaving physicians in a quandary when making a clinical diagnosis of VAP. Enter natural language processing, a tool that is increasingly being applied in radiology as part of machine learning to aid in-text analysis of radiology reports (Med. Image Anal. 2012 [doi:10.1016/j.media.2012.02.005]).

The investigators used natural language processing coding methods to code 1,343 chest x-ray reports from the day prior, day of, and day after BAL among 344 trauma patients ventilated for more than 48 hours at a level 1 trauma center. Two specially trained reviewers coded the reports using the chest x-ray element from the Clinical Pulmonary Infection Score (CPIS) as "no infiltrate," "diffuse infiltrate or atelectasis," or "focal infiltrate" and scored the reports on a three-point scale for suspicion of pneumonia as "no suspicion," "suspicion," or "probable pneumonia."

The CPIS classifier had a 90% overall accuracy, 93% specificity, 86% sensitivity, and 85% positive predictive value. The suspicion classifier achieved comparable results of 85%, 89%, 78%, and 78%, respectively.

As expected, localized infiltrate was significantly more common in reports from BAL-positive than BAL-negative patients (13% vs. 9%), while no infiltrate was significantly more common in those from BAL-negative patients (15.3% vs. 11.5%). However, 1,013 chest x-ray reports, or 75.4% of the data, fell in-between with diffuse infiltrate or atelectasis and had a 50-50 chance of being diagnosed as VAP, Dr. Evans said at the annual meeting of the Surgical Infection Society.

"Failure to discriminate diffuse infiltrate defines the group where culture data is most useful," she observed.

Radiology reports noting any suspicion of pneumonia were significantly more common in positive-BAL than in negative-BAL patients (45.6% vs. 28%), while reports with no suspicion of pneumonia were significantly more common in BAL-negative patients (68% vs. 60%).

Still, 430 (50%) of the 856 chest x-ray reports with no suspicion of VAP were in patients with BAL-positive results, Dr. Evans pointed out.

To sort out the implications of this finding, the investigators stratified the CPIS data by time and discovered that differences between the BAL-positive and -negative groups regarding the presence or absence of infiltrates were statistically significant only on chest x-ray reports from the day after BAL (P = .004).

"Considering the timing of this chest x-ray report information is absolutely crucial and something we will definitely incorporate in the future," she said, adding that future work will involve evaluation of coded chest x-ray report content in VAP risk assessment.

Invited discussant Dr. Addison K. May, chief of trauma and surgical critical care at Vanderbilt University in Nashville, Tenn., questioned whether the authors were surprised by the findings given that chest x-ray readings and BAL results correlate only about 40% of the time, and asked why the authors chose to include the radiology report from the day after BAL. Dr. Evans said the lack of correlation wasn’t surprising and that chest x-ray report language will be incorporated, along with other available clinical values, into their VAP risk assessment model.

"To exclude the chest x-ray information is to ignore a fundamental piece of diagnostic data that clinicians use all the time," she added. "As much as we don’t like to rely on the chest x-ray, I’m currently doing a qualitative study of the diagnosis of ventilator-associated pneumonia at my institution, and I can tell you in the 15 interviews I’ve done, every single person says the chest x-ray is a fundamental piece that they rely on to make the diagnosis.

"So I think if we’re going to remove the chest x-ray from our definition, whether it’s from surveillance or from the definition that we use clinically, we have to have data to support that it shouldn’t be there."

Dr. Evans said the chest x-ray report from the day after BAL was included to help train the classifier to be accurate, and that the finding of statistical significance only for that day’s chest x-ray report data was unexpected and provocative.

Dr. Pamela Lipsett, immediate past president of the Surgical Infection Society, was involved in the CDC’s redefinition of what is now termed ventilator-associated events. She argued against the use of chest x-rays for VAP diagnosis and said they were removed from the CDC definition because they are unreliable.

Some attendees questioned why the authors didn’t just use a structured method for reading the radiographs. Dr. E. Patchen Dellinger, also a past president of the Society, simply asked, "Haven’t you just proved that we don’t know how to diagnosis VAP and that we should stop taking chest x-rays unless we’re worried about a pneumothorax?"

Dr. Evans replied that there are many other indications for chest x-ray in the ICU, but added that "the days of getting a chest x-ray every morning just because the patient is ventilated are a gross overuse of that imaging modality."

The authors reported no relevant conflicts of interest.

DALLAS – Clinicians frequently perform bronchoalveolar lavage in ventilated trauma patients without radiologic evidence of pneumonia, according to a retrospective analysis.

Among 1,343 chest x-ray reports from 344 patients who all underwent bronchoalveolar lavage (BAL), there was no mention of infiltrates in 11% and no suspicion of pneumonia in 64%, according to a review that used natural language processing to sift through the reports.

"Our indication for BAL includes chest x-ray infiltrates or a change in chest x-rays, so I was very surprised to see that there were so many BALs done without an infiltrate mentioned in the chest x-ray report," said lead author Dr. Heather L. Evans, a trauma and acute care surgeon and surgical intensivist at the University of Washington in Seattle. "I think that this may be something of a soft call when providers are concerned that the patient has increasing secretions, increasing oxygenation, and worsening sepsis of unknown etiology. Perhaps the chest x-ray is not as firm and fast a rule as we are led to believe."

Indeed, the Centers for Disease Control and Prevention removed the chest x-ray from its new surveillance definition for what is now termed adult ventilator-associated events. The new definition, expected to be implemented in 2013, is not intended for clinical management, leaving physicians in a quandary when making a clinical diagnosis of VAP. Enter natural language processing, a tool that is increasingly being applied in radiology as part of machine learning to aid in-text analysis of radiology reports (Med. Image Anal. 2012 [doi:10.1016/j.media.2012.02.005]).

The investigators used natural language processing coding methods to code 1,343 chest x-ray reports from the day prior, day of, and day after BAL among 344 trauma patients ventilated for more than 48 hours at a level 1 trauma center. Two specially trained reviewers coded the reports using the chest x-ray element from the Clinical Pulmonary Infection Score (CPIS) as "no infiltrate," "diffuse infiltrate or atelectasis," or "focal infiltrate" and scored the reports on a three-point scale for suspicion of pneumonia as "no suspicion," "suspicion," or "probable pneumonia."

The CPIS classifier had a 90% overall accuracy, 93% specificity, 86% sensitivity, and 85% positive predictive value. The suspicion classifier achieved comparable results of 85%, 89%, 78%, and 78%, respectively.

As expected, localized infiltrate was significantly more common in reports from BAL-positive than BAL-negative patients (13% vs. 9%), while no infiltrate was significantly more common in those from BAL-negative patients (15.3% vs. 11.5%). However, 1,013 chest x-ray reports, or 75.4% of the data, fell in-between with diffuse infiltrate or atelectasis and had a 50-50 chance of being diagnosed as VAP, Dr. Evans said at the annual meeting of the Surgical Infection Society.

"Failure to discriminate diffuse infiltrate defines the group where culture data is most useful," she observed.

Radiology reports noting any suspicion of pneumonia were significantly more common in positive-BAL than in negative-BAL patients (45.6% vs. 28%), while reports with no suspicion of pneumonia were significantly more common in BAL-negative patients (68% vs. 60%).

Still, 430 (50%) of the 856 chest x-ray reports with no suspicion of VAP were in patients with BAL-positive results, Dr. Evans pointed out.

To sort out the implications of this finding, the investigators stratified the CPIS data by time and discovered that differences between the BAL-positive and -negative groups regarding the presence or absence of infiltrates were statistically significant only on chest x-ray reports from the day after BAL (P = .004).

"Considering the timing of this chest x-ray report information is absolutely crucial and something we will definitely incorporate in the future," she said, adding that future work will involve evaluation of coded chest x-ray report content in VAP risk assessment.

Invited discussant Dr. Addison K. May, chief of trauma and surgical critical care at Vanderbilt University in Nashville, Tenn., questioned whether the authors were surprised by the findings given that chest x-ray readings and BAL results correlate only about 40% of the time, and asked why the authors chose to include the radiology report from the day after BAL. Dr. Evans said the lack of correlation wasn’t surprising and that chest x-ray report language will be incorporated, along with other available clinical values, into their VAP risk assessment model.

"To exclude the chest x-ray information is to ignore a fundamental piece of diagnostic data that clinicians use all the time," she added. "As much as we don’t like to rely on the chest x-ray, I’m currently doing a qualitative study of the diagnosis of ventilator-associated pneumonia at my institution, and I can tell you in the 15 interviews I’ve done, every single person says the chest x-ray is a fundamental piece that they rely on to make the diagnosis.

"So I think if we’re going to remove the chest x-ray from our definition, whether it’s from surveillance or from the definition that we use clinically, we have to have data to support that it shouldn’t be there."

Dr. Evans said the chest x-ray report from the day after BAL was included to help train the classifier to be accurate, and that the finding of statistical significance only for that day’s chest x-ray report data was unexpected and provocative.

Dr. Pamela Lipsett, immediate past president of the Surgical Infection Society, was involved in the CDC’s redefinition of what is now termed ventilator-associated events. She argued against the use of chest x-rays for VAP diagnosis and said they were removed from the CDC definition because they are unreliable.

Some attendees questioned why the authors didn’t just use a structured method for reading the radiographs. Dr. E. Patchen Dellinger, also a past president of the Society, simply asked, "Haven’t you just proved that we don’t know how to diagnosis VAP and that we should stop taking chest x-rays unless we’re worried about a pneumothorax?"

Dr. Evans replied that there are many other indications for chest x-ray in the ICU, but added that "the days of getting a chest x-ray every morning just because the patient is ventilated are a gross overuse of that imaging modality."

The authors reported no relevant conflicts of interest.