Amy Karon

A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.

Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).

©Sebastian Kaulitzki/thinkstockphotos.com

The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.

The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.

The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.

Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.

A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.

The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.

A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.

Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).

©Sebastian Kaulitzki/thinkstockphotos.com

The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.

The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.

The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.

Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.

A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.

The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.

A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.

Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).

©Sebastian Kaulitzki/thinkstockphotos.com

The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.

The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.

The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.

Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.

A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.

The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.

Only 1.9% of tumor patients who did not have prophylactic antibiotics developed febrile urinary tract infections after flexible cystoscopy, according to research published in the April issue of European Urology.

Even when patients presented with asymptomatic bacteriuria, less than 5% developed UTIs after cystoscopy, said Dr. Harry W. Herr, a urologist at Memorial Sloan-Kettering Cancer Center in New York.

When UTIs occurred, they resolved within 24 hours of starting oral antibiotic therapy and did not involve bacterial sepsis, he reported (Eur. Urol. 2014;65:839-42).

"These data strengthen European guidelines on urologic infections, which state that antibiotic prophylaxis is not recommended before cystoscopy in standard cases," said Dr. Herr. "However, the data also justify avoiding antibiotics in bacteriuric patients."

The prospective registry study enrolled consecutive outpatients with bladder cancer. Patients submitted voided urine samples for culture prior to undergoing flexible cystoscopy, and received no antibiotics before or immediately after. Dr. Herr defined significant bacteriuria as a single-organism culture of greater than 10⁴ colony-forming units per milliliter, and febrile UTI as dysuria and temperature greater than 38° C, or receiving antibiotics from an outside physician for urinary tract symptoms.

Among the 2,010 patients, 489 (24%) had asymptomatic bacteriuria, while 1,521 (76%) had sterile urine, Dr. Herr reported. Thirty-nine patients (1.9%) developed febrile UTI within 30 days of cystoscopy, including 1.1% of noncolonized patients and 4.5% of colonized patients (P = .02).

Cystoscopy is common, and bladder cancer patients have variable risk factors for UTI, so "urologists may need to accept a 4.5% risk of symptomatic UTI to practice antibiotic stewardship by avoiding the overuse (misuse) of unnecessary antibiotics," wrote Dr. Herr.

He relied on patients to self-report UTI and related factors after their first week of follow-up, but he said that this limitation probably did not lead to underdetection of UTIs because most infections develop within several days of cystoscopy.

"It is the responsibility of all physicians to practice antibiotic stewardship and to avoid the unnecessary use of antibiotics where justified," Dr. Herr added. "The current robust data should persuade urologists to do their part."

The study received no funding support, and Dr. Herr reported that he had no conflicts of interest.

Only 1.9% of tumor patients who did not have prophylactic antibiotics developed febrile urinary tract infections after flexible cystoscopy, according to research published in the April issue of European Urology.

Even when patients presented with asymptomatic bacteriuria, less than 5% developed UTIs after cystoscopy, said Dr. Harry W. Herr, a urologist at Memorial Sloan-Kettering Cancer Center in New York.

When UTIs occurred, they resolved within 24 hours of starting oral antibiotic therapy and did not involve bacterial sepsis, he reported (Eur. Urol. 2014;65:839-42).

"These data strengthen European guidelines on urologic infections, which state that antibiotic prophylaxis is not recommended before cystoscopy in standard cases," said Dr. Herr. "However, the data also justify avoiding antibiotics in bacteriuric patients."

The prospective registry study enrolled consecutive outpatients with bladder cancer. Patients submitted voided urine samples for culture prior to undergoing flexible cystoscopy, and received no antibiotics before or immediately after. Dr. Herr defined significant bacteriuria as a single-organism culture of greater than 10⁴ colony-forming units per milliliter, and febrile UTI as dysuria and temperature greater than 38° C, or receiving antibiotics from an outside physician for urinary tract symptoms.

Among the 2,010 patients, 489 (24%) had asymptomatic bacteriuria, while 1,521 (76%) had sterile urine, Dr. Herr reported. Thirty-nine patients (1.9%) developed febrile UTI within 30 days of cystoscopy, including 1.1% of noncolonized patients and 4.5% of colonized patients (P = .02).

Cystoscopy is common, and bladder cancer patients have variable risk factors for UTI, so "urologists may need to accept a 4.5% risk of symptomatic UTI to practice antibiotic stewardship by avoiding the overuse (misuse) of unnecessary antibiotics," wrote Dr. Herr.

He relied on patients to self-report UTI and related factors after their first week of follow-up, but he said that this limitation probably did not lead to underdetection of UTIs because most infections develop within several days of cystoscopy.

"It is the responsibility of all physicians to practice antibiotic stewardship and to avoid the unnecessary use of antibiotics where justified," Dr. Herr added. "The current robust data should persuade urologists to do their part."

The study received no funding support, and Dr. Herr reported that he had no conflicts of interest.

Only 1.9% of tumor patients who did not have prophylactic antibiotics developed febrile urinary tract infections after flexible cystoscopy, according to research published in the April issue of European Urology.

Even when patients presented with asymptomatic bacteriuria, less than 5% developed UTIs after cystoscopy, said Dr. Harry W. Herr, a urologist at Memorial Sloan-Kettering Cancer Center in New York.

When UTIs occurred, they resolved within 24 hours of starting oral antibiotic therapy and did not involve bacterial sepsis, he reported (Eur. Urol. 2014;65:839-42).

"These data strengthen European guidelines on urologic infections, which state that antibiotic prophylaxis is not recommended before cystoscopy in standard cases," said Dr. Herr. "However, the data also justify avoiding antibiotics in bacteriuric patients."

The prospective registry study enrolled consecutive outpatients with bladder cancer. Patients submitted voided urine samples for culture prior to undergoing flexible cystoscopy, and received no antibiotics before or immediately after. Dr. Herr defined significant bacteriuria as a single-organism culture of greater than 10⁴ colony-forming units per milliliter, and febrile UTI as dysuria and temperature greater than 38° C, or receiving antibiotics from an outside physician for urinary tract symptoms.

Among the 2,010 patients, 489 (24%) had asymptomatic bacteriuria, while 1,521 (76%) had sterile urine, Dr. Herr reported. Thirty-nine patients (1.9%) developed febrile UTI within 30 days of cystoscopy, including 1.1% of noncolonized patients and 4.5% of colonized patients (P = .02).

Cystoscopy is common, and bladder cancer patients have variable risk factors for UTI, so "urologists may need to accept a 4.5% risk of symptomatic UTI to practice antibiotic stewardship by avoiding the overuse (misuse) of unnecessary antibiotics," wrote Dr. Herr.

He relied on patients to self-report UTI and related factors after their first week of follow-up, but he said that this limitation probably did not lead to underdetection of UTIs because most infections develop within several days of cystoscopy.

"It is the responsibility of all physicians to practice antibiotic stewardship and to avoid the unnecessary use of antibiotics where justified," Dr. Herr added. "The current robust data should persuade urologists to do their part."

The study received no funding support, and Dr. Herr reported that he had no conflicts of interest.

Routine screening for prostate cancer decreased in Ohio after the U.S. Preventive Services Task Force recommended against it, with a more immediate and pronounced decrease in the urban/academic setting and a less gradual change in suburban and rural settings, researchers reported online in the Journal of Urology.

The decreases in ordering the test were observed in all specialties, the investigators reported. "Interestingly, the greatest impact was seen among urologists," said Dr. Robert Abouassaly and his associates at University Hospitals Case Medical Center, Cleveland.

The incidence of diagnosed prostate cancer rose dramatically in the United States after the Food and Drug Administration approved routine PSA screening in men aged 50 years and older. With that increase came debate about possible overdiagnosis and overtreatment of "clinically insignificant" prostate cancer, the investigators said (J. Urol. 2013 [doi:10.1016/j.juro.2013.12.010]).

Screening trial results published in 2009 led the USPSTF to recommend against routine PSA testing in May 2012, saying the potential risks outweighed the benefits. To assess the impact of the task force recommendations, Dr. Abouassaly and his colleagues performed a regression analysis of all PSA screening tests (n = 43,498) at University Hospitals Case Medical Center and affiliated hospitals in Northeastern Ohio from January 2008 to December 2012.

They found that testing of men aged 50 and older increased significantly across all fields of practice until the first screening trial results were published in March 2009 (P less than .001). After that, screening decreased significantly until May 2012 (P less than .001), when the USPSTF recommendations were published. Screening continued to decrease after that, but the decrease was nonsignificant.

Specialists in internal medicine ordered the most tests (64.9%), followed by family medicine (23.7%), urology (6.1%), and hematology/oncology (1.3%), the investigators said.

Ordering of the screening test declined most at an urban teaching hospital and among urologists, for whom "prostate cancer is a focal point of daily practice," the researchers added.

"Overall we believe that although we detected a statistically significant decrease in PSA use with time, the absolute decrease was small and the clinical significance of our findings is uncertain," said Dr. Abouassaly and his associates. Further studies should investigate the recommendation’s effects on screening, diagnosis, treatment, and prognosis of prostate cancer, they said.

A National Institute of Diabetes and Digestive and Kidney Diseases award supported the study. No investigator disclosures were reported.

Routine screening for prostate cancer decreased in Ohio after the U.S. Preventive Services Task Force recommended against it, with a more immediate and pronounced decrease in the urban/academic setting and a less gradual change in suburban and rural settings, researchers reported online in the Journal of Urology.

The decreases in ordering the test were observed in all specialties, the investigators reported. "Interestingly, the greatest impact was seen among urologists," said Dr. Robert Abouassaly and his associates at University Hospitals Case Medical Center, Cleveland.

The incidence of diagnosed prostate cancer rose dramatically in the United States after the Food and Drug Administration approved routine PSA screening in men aged 50 years and older. With that increase came debate about possible overdiagnosis and overtreatment of "clinically insignificant" prostate cancer, the investigators said (J. Urol. 2013 [doi:10.1016/j.juro.2013.12.010]).

Screening trial results published in 2009 led the USPSTF to recommend against routine PSA testing in May 2012, saying the potential risks outweighed the benefits. To assess the impact of the task force recommendations, Dr. Abouassaly and his colleagues performed a regression analysis of all PSA screening tests (n = 43,498) at University Hospitals Case Medical Center and affiliated hospitals in Northeastern Ohio from January 2008 to December 2012.

They found that testing of men aged 50 and older increased significantly across all fields of practice until the first screening trial results were published in March 2009 (P less than .001). After that, screening decreased significantly until May 2012 (P less than .001), when the USPSTF recommendations were published. Screening continued to decrease after that, but the decrease was nonsignificant.

Specialists in internal medicine ordered the most tests (64.9%), followed by family medicine (23.7%), urology (6.1%), and hematology/oncology (1.3%), the investigators said.

Ordering of the screening test declined most at an urban teaching hospital and among urologists, for whom "prostate cancer is a focal point of daily practice," the researchers added.

"Overall we believe that although we detected a statistically significant decrease in PSA use with time, the absolute decrease was small and the clinical significance of our findings is uncertain," said Dr. Abouassaly and his associates. Further studies should investigate the recommendation’s effects on screening, diagnosis, treatment, and prognosis of prostate cancer, they said.

A National Institute of Diabetes and Digestive and Kidney Diseases award supported the study. No investigator disclosures were reported.

Routine screening for prostate cancer decreased in Ohio after the U.S. Preventive Services Task Force recommended against it, with a more immediate and pronounced decrease in the urban/academic setting and a less gradual change in suburban and rural settings, researchers reported online in the Journal of Urology.

The decreases in ordering the test were observed in all specialties, the investigators reported. "Interestingly, the greatest impact was seen among urologists," said Dr. Robert Abouassaly and his associates at University Hospitals Case Medical Center, Cleveland.

The incidence of diagnosed prostate cancer rose dramatically in the United States after the Food and Drug Administration approved routine PSA screening in men aged 50 years and older. With that increase came debate about possible overdiagnosis and overtreatment of "clinically insignificant" prostate cancer, the investigators said (J. Urol. 2013 [doi:10.1016/j.juro.2013.12.010]).

Screening trial results published in 2009 led the USPSTF to recommend against routine PSA testing in May 2012, saying the potential risks outweighed the benefits. To assess the impact of the task force recommendations, Dr. Abouassaly and his colleagues performed a regression analysis of all PSA screening tests (n = 43,498) at University Hospitals Case Medical Center and affiliated hospitals in Northeastern Ohio from January 2008 to December 2012.

They found that testing of men aged 50 and older increased significantly across all fields of practice until the first screening trial results were published in March 2009 (P less than .001). After that, screening decreased significantly until May 2012 (P less than .001), when the USPSTF recommendations were published. Screening continued to decrease after that, but the decrease was nonsignificant.

Specialists in internal medicine ordered the most tests (64.9%), followed by family medicine (23.7%), urology (6.1%), and hematology/oncology (1.3%), the investigators said.

Ordering of the screening test declined most at an urban teaching hospital and among urologists, for whom "prostate cancer is a focal point of daily practice," the researchers added.

"Overall we believe that although we detected a statistically significant decrease in PSA use with time, the absolute decrease was small and the clinical significance of our findings is uncertain," said Dr. Abouassaly and his associates. Further studies should investigate the recommendation’s effects on screening, diagnosis, treatment, and prognosis of prostate cancer, they said.

A National Institute of Diabetes and Digestive and Kidney Diseases award supported the study. No investigator disclosures were reported.

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.

The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).

The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.

Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.

Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.

The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.

The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.

The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.

cardnews@frontlinemedcom.com

A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.

The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).

The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.

Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.

Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.

The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.

The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.

The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.

cardnews@frontlinemedcom.com

A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.

The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).

The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.

Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.

Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.

The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.

The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.

The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.

cardnews@frontlinemedcom.com

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Variability in coding of pneumonia cases skewed risk-standardized mortality rates and hospital performance rankings, investigators reported online March 17.

The bias could impede efforts to compare quality of care among hospitals, Dr. Michael Rothberg of the Cleveland Clinic in Ohio and his associates said (Ann. Int. Med. Mar. 17 [doi: 10.7326/M13-1419]).

The Centers for Medicare & Medicaid Services partially based hospital reimbursements on 30-day risk-standardized mortality rates. To exclude nosocomial pneumonia cases, CMS included only patients with a primary diagnosis of pneumonia when estimating 30-day risk-standardized pneumonia mortality rates.

But over time, hospitals changed how they coded the sickest patients with pneumonia, Dr. Rothberg and his associates said. These patients increasingly received a principal diagnosis of sepsis or organ failure, instead of pneumonia, and thus were excluded from mortality estimates.

"These events gave the false impression that pneumonia outcomes had improved more than they had," they said, adding that "just as changes in coding over time could lead to erroneous conclusions about decreasing mortality rates, variation in coding across hospitals could lead to biased estimates of their relative mortality rates."

The investigators conducted a cross-sectional study of more than 250,000 hospitalizations of adults with a principal or secondary diagnosis of pneumonia at 329 U.S. hospitals between 2007 and 2010.

When the definition of pneumonia excluded patients with primary sepsis or respiratory failure, 4.3% of hospitals had mortality rates that were significantly better than the mean, and 6.4% had rates that were significantly worse. But when the expanded definition was used, 12% of hospitals had mortality rates that were better than the mean, while 23% had rates that were worse. Performance ranking changed for 28% of hospitals.

When the expanded case definition was used, outlier status worsened for 41% of the hospitals with the highest proportions of patients with primary sepsis or respiratory failure, but improved for 20% and worsened for none of the hospitals with the lowest proportions of these patients.

"Efforts to broaden the scope of hospital performance measures from the initial set of measures based on processes to those focused on patient outcomes are laudable, but caution is required," the investigators said. "Misclassification could harm individual hospitals and weaken confidence in public reporting."

Adding principal diagnoses of respiratory failure or sepsis with secondary pneumonia to the definition of pneumonia could help lessen the biases, they said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Rothberg and Dr. Lindenaur also received grants from AHRQ.

*Correction, 3/19/2014: An earlier version of this story misstated the name of Dr. Scott A. Flanders, one of the editorialists.

Variability in coding of pneumonia cases skewed risk-standardized mortality rates and hospital performance rankings, investigators reported online March 17.

The bias could impede efforts to compare quality of care among hospitals, Dr. Michael Rothberg of the Cleveland Clinic in Ohio and his associates said (Ann. Int. Med. Mar. 17 [doi: 10.7326/M13-1419]).

The Centers for Medicare & Medicaid Services partially based hospital reimbursements on 30-day risk-standardized mortality rates. To exclude nosocomial pneumonia cases, CMS included only patients with a primary diagnosis of pneumonia when estimating 30-day risk-standardized pneumonia mortality rates.

But over time, hospitals changed how they coded the sickest patients with pneumonia, Dr. Rothberg and his associates said. These patients increasingly received a principal diagnosis of sepsis or organ failure, instead of pneumonia, and thus were excluded from mortality estimates.

"These events gave the false impression that pneumonia outcomes had improved more than they had," they said, adding that "just as changes in coding over time could lead to erroneous conclusions about decreasing mortality rates, variation in coding across hospitals could lead to biased estimates of their relative mortality rates."

The investigators conducted a cross-sectional study of more than 250,000 hospitalizations of adults with a principal or secondary diagnosis of pneumonia at 329 U.S. hospitals between 2007 and 2010.

When the definition of pneumonia excluded patients with primary sepsis or respiratory failure, 4.3% of hospitals had mortality rates that were significantly better than the mean, and 6.4% had rates that were significantly worse. But when the expanded definition was used, 12% of hospitals had mortality rates that were better than the mean, while 23% had rates that were worse. Performance ranking changed for 28% of hospitals.

When the expanded case definition was used, outlier status worsened for 41% of the hospitals with the highest proportions of patients with primary sepsis or respiratory failure, but improved for 20% and worsened for none of the hospitals with the lowest proportions of these patients.

"Efforts to broaden the scope of hospital performance measures from the initial set of measures based on processes to those focused on patient outcomes are laudable, but caution is required," the investigators said. "Misclassification could harm individual hospitals and weaken confidence in public reporting."

Adding principal diagnoses of respiratory failure or sepsis with secondary pneumonia to the definition of pneumonia could help lessen the biases, they said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Rothberg and Dr. Lindenaur also received grants from AHRQ.

*Correction, 3/19/2014: An earlier version of this story misstated the name of Dr. Scott A. Flanders, one of the editorialists.

Variability in coding of pneumonia cases skewed risk-standardized mortality rates and hospital performance rankings, investigators reported online March 17.

The bias could impede efforts to compare quality of care among hospitals, Dr. Michael Rothberg of the Cleveland Clinic in Ohio and his associates said (Ann. Int. Med. Mar. 17 [doi: 10.7326/M13-1419]).

The Centers for Medicare & Medicaid Services partially based hospital reimbursements on 30-day risk-standardized mortality rates. To exclude nosocomial pneumonia cases, CMS included only patients with a primary diagnosis of pneumonia when estimating 30-day risk-standardized pneumonia mortality rates.

But over time, hospitals changed how they coded the sickest patients with pneumonia, Dr. Rothberg and his associates said. These patients increasingly received a principal diagnosis of sepsis or organ failure, instead of pneumonia, and thus were excluded from mortality estimates.

"These events gave the false impression that pneumonia outcomes had improved more than they had," they said, adding that "just as changes in coding over time could lead to erroneous conclusions about decreasing mortality rates, variation in coding across hospitals could lead to biased estimates of their relative mortality rates."

The investigators conducted a cross-sectional study of more than 250,000 hospitalizations of adults with a principal or secondary diagnosis of pneumonia at 329 U.S. hospitals between 2007 and 2010.

When the definition of pneumonia excluded patients with primary sepsis or respiratory failure, 4.3% of hospitals had mortality rates that were significantly better than the mean, and 6.4% had rates that were significantly worse. But when the expanded definition was used, 12% of hospitals had mortality rates that were better than the mean, while 23% had rates that were worse. Performance ranking changed for 28% of hospitals.

When the expanded case definition was used, outlier status worsened for 41% of the hospitals with the highest proportions of patients with primary sepsis or respiratory failure, but improved for 20% and worsened for none of the hospitals with the lowest proportions of these patients.

"Efforts to broaden the scope of hospital performance measures from the initial set of measures based on processes to those focused on patient outcomes are laudable, but caution is required," the investigators said. "Misclassification could harm individual hospitals and weaken confidence in public reporting."

Adding principal diagnoses of respiratory failure or sepsis with secondary pneumonia to the definition of pneumonia could help lessen the biases, they said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Rothberg and Dr. Lindenaur also received grants from AHRQ.

*Correction, 3/19/2014: An earlier version of this story misstated the name of Dr. Scott A. Flanders, one of the editorialists.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Cancer patients who received palliative chemotherapy at the end of life were significantly more likely to undergo intensive medical care and to die in an ICU, according to researchers.

These patients were also significantly more likely to be referred late to hospice care compared with terminal patients who did not receive palliative chemotherapy, said Dr. Holly Prigerson of Weill Cornell Medical College, New York, and her associates.

The prospective, multicenter cohort study enrolled 386 adults with metastatic cancers refractory to at least one chemotherapy regimen. Patients were terminally ill at enrollment. In all, 216 (56%) were receiving palliative chemotherapy when they enrolled a median of 4 months before death.

Fourteen percent of patients receiving palliative chemotherapy underwent mechanical ventilation, cardiopulmonary resuscitation, or both in the week before death, compared with 2% of patients not receiving palliative chemotherapy. The adjusted difference in risk was 10.5%. Since events were rare, adjusted risk differences were calculated and reported instead of odds ratios, as odds ratios might have exaggerated actual risk, the investigators noted.

Patients receiving palliative chemotherapy were less likely to acknowledge that their illness was terminal (35% vs. 49%, P = .04) and to report having discussed their end-of-life wishes with a physician (37% vs. 48%, P = .03. They were also less likely to have completed a do-not-resuscitate order compared with patients not receiving palliative chemotherapy (36% vs. 49%, P less than .05), the investigators reported (BMJ 2014 [doi: 10.1136/bmj.g1219]).

There was no significant difference in overall survival between patients who received palliative chemotherapy and those who did not (hazard ratio 1.11), the investigators said.

The findings show that "end of life discussions may be particularly important for patients receiving palliative chemotherapy, who should be informed by data on the likely outcomes associated with its use," the researchers said.

The study was nonrandomized, and therefore patients who received palliative chemotherapy could have differed in terms of unmeasured factors such as disease duration, the investigators noted. They recommended larger studies to confirm their findings.

The authors received research support from the National Institute of Mental Health, the National Cancer Institute, the American Cancer Society, and the Conquer Cancer Foundation. No authors reported conflicts of interest.

Cancer patients who received palliative chemotherapy at the end of life were significantly more likely to undergo intensive medical care and to die in an ICU, according to researchers.

These patients were also significantly more likely to be referred late to hospice care compared with terminal patients who did not receive palliative chemotherapy, said Dr. Holly Prigerson of Weill Cornell Medical College, New York, and her associates.

The prospective, multicenter cohort study enrolled 386 adults with metastatic cancers refractory to at least one chemotherapy regimen. Patients were terminally ill at enrollment. In all, 216 (56%) were receiving palliative chemotherapy when they enrolled a median of 4 months before death.

Fourteen percent of patients receiving palliative chemotherapy underwent mechanical ventilation, cardiopulmonary resuscitation, or both in the week before death, compared with 2% of patients not receiving palliative chemotherapy. The adjusted difference in risk was 10.5%. Since events were rare, adjusted risk differences were calculated and reported instead of odds ratios, as odds ratios might have exaggerated actual risk, the investigators noted.

Patients receiving palliative chemotherapy were less likely to acknowledge that their illness was terminal (35% vs. 49%, P = .04) and to report having discussed their end-of-life wishes with a physician (37% vs. 48%, P = .03. They were also less likely to have completed a do-not-resuscitate order compared with patients not receiving palliative chemotherapy (36% vs. 49%, P less than .05), the investigators reported (BMJ 2014 [doi: 10.1136/bmj.g1219]).

There was no significant difference in overall survival between patients who received palliative chemotherapy and those who did not (hazard ratio 1.11), the investigators said.

The findings show that "end of life discussions may be particularly important for patients receiving palliative chemotherapy, who should be informed by data on the likely outcomes associated with its use," the researchers said.

The study was nonrandomized, and therefore patients who received palliative chemotherapy could have differed in terms of unmeasured factors such as disease duration, the investigators noted. They recommended larger studies to confirm their findings.

The authors received research support from the National Institute of Mental Health, the National Cancer Institute, the American Cancer Society, and the Conquer Cancer Foundation. No authors reported conflicts of interest.

Cancer patients who received palliative chemotherapy at the end of life were significantly more likely to undergo intensive medical care and to die in an ICU, according to researchers.

These patients were also significantly more likely to be referred late to hospice care compared with terminal patients who did not receive palliative chemotherapy, said Dr. Holly Prigerson of Weill Cornell Medical College, New York, and her associates.

The prospective, multicenter cohort study enrolled 386 adults with metastatic cancers refractory to at least one chemotherapy regimen. Patients were terminally ill at enrollment. In all, 216 (56%) were receiving palliative chemotherapy when they enrolled a median of 4 months before death.

Fourteen percent of patients receiving palliative chemotherapy underwent mechanical ventilation, cardiopulmonary resuscitation, or both in the week before death, compared with 2% of patients not receiving palliative chemotherapy. The adjusted difference in risk was 10.5%. Since events were rare, adjusted risk differences were calculated and reported instead of odds ratios, as odds ratios might have exaggerated actual risk, the investigators noted.

Patients receiving palliative chemotherapy were less likely to acknowledge that their illness was terminal (35% vs. 49%, P = .04) and to report having discussed their end-of-life wishes with a physician (37% vs. 48%, P = .03. They were also less likely to have completed a do-not-resuscitate order compared with patients not receiving palliative chemotherapy (36% vs. 49%, P less than .05), the investigators reported (BMJ 2014 [doi: 10.1136/bmj.g1219]).

There was no significant difference in overall survival between patients who received palliative chemotherapy and those who did not (hazard ratio 1.11), the investigators said.

The findings show that "end of life discussions may be particularly important for patients receiving palliative chemotherapy, who should be informed by data on the likely outcomes associated with its use," the researchers said.

The study was nonrandomized, and therefore patients who received palliative chemotherapy could have differed in terms of unmeasured factors such as disease duration, the investigators noted. They recommended larger studies to confirm their findings.

The authors received research support from the National Institute of Mental Health, the National Cancer Institute, the American Cancer Society, and the Conquer Cancer Foundation. No authors reported conflicts of interest.