Sharon Worcester

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.

Compared with on-pump coronary artery bypass graft surgery, off-pump CABG reduced the risk of postoperative acute kidney injury, but was not associated with better-preserved kidney function at 1 year in a substudy of the randomized CORONARY trial.

Acute kidney injury within 30 days of surgery occurred in 17.5% of 1,472 patients in the off-pump group, compared with 20.8% of 1,460 in the on-pump group (relative risk, 0.83). Loss of kidney function at 1 year occurred in 17.1% and 15.3% of patients in the groups, respectively (relative risk, 1.10), Dr. Amit X. Garg of the London (Ontario)Health Sciences Center, and his colleagues reported on behalf of the CORONARY (Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularization Study) investigators.

The observed relative risks for both acute kidney injury and long-term loss of kidney function were consistent when the data were reanalyzed using multiple alternate definitions of the two outcomes, as well as when using the composite outcomes of acute kidney injury or death, or kidney function loss or death, respectively, the authors said.

The findings were presented at the annual European Renal Association-European Dialysis and Transplant Association Congress, and were published simultaneously in JAMA.

CORONARY participants were 4,732 adults undergoing first isolated CABG surgery at 79 sites in 19 countries. Previously published results from the CORONARY trial showed no significant difference between on- and off-pump CABG with respect to a composite outcome of death, nonfatal myocardial infarction, stroke or new dialysis for kidney failure (or in any of these individual components) within 30 days or at 1 year postrandomization. Those included in the current analysis were 2,932 patients from 63 sites in 16 countries who were enrolled into the kidney function substudy between January, 2010 and November, 2011.

Acute kidney injury was defined as an increase of at least 50% in serum creatinine concentration from prerandomization. Loss of kidney function at 1 year was defined as at least a 20% loss in estimated glomerular filtration rate from prerandomization level, the investigators said (JAMA 2014 June 2[doi:10.1001/jama.2014.4952]).

The current findings, along with those from a recent meta-analysis of 22 prior randomized, controlled trials provide convincing evidence that off-pump vs. on-pump CABG surgery reduces the risk of mild to moderate acute kidney injury, particularly in those with preoperative chronic kidney disease, they said.

Mild or moderate acute kidney injury affects about 30% of patients after cardiac surgery, with about 1% requiring acute dialysis for severe kidney injury, but the effects of mild or moderate acute kidney injury on long-term kidney function are not clear.

Animal studies have suggested a causal link, and several human observational studies have shown a link as early as 3 months after injury, but "it remains unproven in a randomized clinical trial that an intervention that prevents such acute kidney injury better preserves long-term kidney function," they said.

The lack of an effect on long-term kidney function in the CORONARY trial may reflect inadequate follow-up, errors with serum creatinine concentration as a measure of kidney function, nonacute kidney injury effects of off-pump CABG surgery or differential care in follow-up between the groups, small magnitude of injury reduction with off-pump CABG, or lack of association between mild to moderate acute kidney injury and substantial chronic kidney disease.

"Regardless of the reason attributed to the observed 1-year kidney results from the CORONARY trial, the findings emphasize proof is needed to claim an intervention that reduces the risk of mild acute kidney injury better preserves long-term kidney function for the group that received it," the investigators wrote, adding that this has implications for the development, testing, and use of interventions to prevent acute kidney injury.

The findings support the current position of regulatory agencies – including the Food and Drug Administration – that no intervention will be approved based solely on its ability to prevent modest acute kidney injury, but rather that proof is required that the intervention has an effect on long-term permanent kidney function or other clinically meaningful events, they explained.

"This provides pause for interventions such as N-acetylcysteine and intravenous sodium bicarbonate, which have been broadly adopted because smaller trials demonstrated a reduced risk of modest acute kidney injury without proof of an effect on permanent kidney function. Our results also have implications for trials currently examining intervention effects on mild acute kidney injury without assessing long-term kidney function," they concluded. Furthermore, future trials should consider multiple measures of kidney function over time, examine trajectories of kidney function loss, and use new markers of kidney function or injury, and enroll a greater number of patients with baseline chronic kidney disease to better ascertain whether a causal relationship exists between acute kidney injury and long-term kidney function, they said.

CORONARY and the kidney substudy were supported by grants from the Canadian Institutes of Health Research.

Dr. Garg reported receiving grant funding from Astellas, Roche, and Pfizer. Another author (Dr. P.J. Devereaux) reported receiving grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Roche Diagnostics, and Stryker, and one (Dr. Chirag R. Parikh) reported participating on a data monitoring committee for a phase II trial sponsored by AbbVie. The remaining authors reported having no disclosures.

CHICAGO – A four-item pregnancy-specific sleep disturbance scale proved valid as a screening tool for sleep-disordered breathing in pregnancy, and was associated with preeclampsia in a study of more than 1,100 women.

After adjustment for potential confounders – including sociodemographics, body mass index, and high blood pressure – a higher score on the short-form pregnancy-specific questionnaire (SF-SPQ) was significantly associated with an increase in the risk of preeclampsia (adjusted risk ratio, 1.54) Alpna Agrawal, Ph.D., of the University of Texas Health Science Center, Houston, reported in a poster at the annual meeting of the American Congress of Obstetricians and Gynecologists.

"In a clinical setting, the short format and validity of SF-SPQ shown in this study suggests it may be a quick and effective method to screen women at risk for sleep-disordered breathing," Dr. Agrawal wrote.

The SF-SPQ was developed based on data collected from 1,153 pregnant women seen in three outpatient clinics between 2010 and 2013. Sleep patterns were assessed by the Berlin Questionnaire, Epworth Sleepiness Scale, and by questions regarding napping behavior. A confirmatory factor analysis (CFA) was performed to develop a sensitive and specific sleep scale derived from the findings. The scale ultimately included "snoring frequently," "bothersome snoring," "stopped breathing while sleeping," and "falling asleep while driving."

"These items were conceptually related to sleep-disordered breathing during pregnancy, statistically intercorrelated, and/or associated with adverse outcomes. CFA factor loadings were significant and model fit was good," Dr. Agrawal wrote.

In addition to higher score on the SF-SPQ, adjusted relative risks of adverse outcomes were associated with BMI greater than 30 (adjusted relative risk, 1.55), hypertension (adjusted RR, 5.07), and screening positive on the Berlin Questionnaire (adjusted RR, 2.45).

"These data suggest that comorbid conditions such as obesity and hypertension (which are themselves a part of the Berlin Questionnaire) drive association with pregnancy outcomes. However, preeclampsia was independently associated with the SF-SPQ," Dr. Agrawal noted.

Prior studies have demonstrated that sleep-disordered breathing during pregnancy is associated with adverse pregnancy outcomes, but an efficient and efficacious screening tool for sleep disorders has been lacking.

The findings are important, because in the United States, preeclampsia affects up to 6% of pregnancies and is linked with other morbidities such as intrauterine growth restriction, and because studies suggest that the use of continuous positive airway pressure (CPAP) can reduce the risk of preeclampsia in pregnant patients with sleep-disordered breathing.

Additional research is needed to evaluate the efficacy of the SF-SPQ for detecting women at risk, Dr. Agrawal concluded.

Dr. Agrawal reported having no disclosures.

CHICAGO – A four-item pregnancy-specific sleep disturbance scale proved valid as a screening tool for sleep-disordered breathing in pregnancy, and was associated with preeclampsia in a study of more than 1,100 women.

After adjustment for potential confounders – including sociodemographics, body mass index, and high blood pressure – a higher score on the short-form pregnancy-specific questionnaire (SF-SPQ) was significantly associated with an increase in the risk of preeclampsia (adjusted risk ratio, 1.54) Alpna Agrawal, Ph.D., of the University of Texas Health Science Center, Houston, reported in a poster at the annual meeting of the American Congress of Obstetricians and Gynecologists.

"In a clinical setting, the short format and validity of SF-SPQ shown in this study suggests it may be a quick and effective method to screen women at risk for sleep-disordered breathing," Dr. Agrawal wrote.

The SF-SPQ was developed based on data collected from 1,153 pregnant women seen in three outpatient clinics between 2010 and 2013. Sleep patterns were assessed by the Berlin Questionnaire, Epworth Sleepiness Scale, and by questions regarding napping behavior. A confirmatory factor analysis (CFA) was performed to develop a sensitive and specific sleep scale derived from the findings. The scale ultimately included "snoring frequently," "bothersome snoring," "stopped breathing while sleeping," and "falling asleep while driving."

"These items were conceptually related to sleep-disordered breathing during pregnancy, statistically intercorrelated, and/or associated with adverse outcomes. CFA factor loadings were significant and model fit was good," Dr. Agrawal wrote.

In addition to higher score on the SF-SPQ, adjusted relative risks of adverse outcomes were associated with BMI greater than 30 (adjusted relative risk, 1.55), hypertension (adjusted RR, 5.07), and screening positive on the Berlin Questionnaire (adjusted RR, 2.45).

"These data suggest that comorbid conditions such as obesity and hypertension (which are themselves a part of the Berlin Questionnaire) drive association with pregnancy outcomes. However, preeclampsia was independently associated with the SF-SPQ," Dr. Agrawal noted.

Prior studies have demonstrated that sleep-disordered breathing during pregnancy is associated with adverse pregnancy outcomes, but an efficient and efficacious screening tool for sleep disorders has been lacking.

The findings are important, because in the United States, preeclampsia affects up to 6% of pregnancies and is linked with other morbidities such as intrauterine growth restriction, and because studies suggest that the use of continuous positive airway pressure (CPAP) can reduce the risk of preeclampsia in pregnant patients with sleep-disordered breathing.

Additional research is needed to evaluate the efficacy of the SF-SPQ for detecting women at risk, Dr. Agrawal concluded.

Dr. Agrawal reported having no disclosures.

CHICAGO – A four-item pregnancy-specific sleep disturbance scale proved valid as a screening tool for sleep-disordered breathing in pregnancy, and was associated with preeclampsia in a study of more than 1,100 women.

After adjustment for potential confounders – including sociodemographics, body mass index, and high blood pressure – a higher score on the short-form pregnancy-specific questionnaire (SF-SPQ) was significantly associated with an increase in the risk of preeclampsia (adjusted risk ratio, 1.54) Alpna Agrawal, Ph.D., of the University of Texas Health Science Center, Houston, reported in a poster at the annual meeting of the American Congress of Obstetricians and Gynecologists.

"In a clinical setting, the short format and validity of SF-SPQ shown in this study suggests it may be a quick and effective method to screen women at risk for sleep-disordered breathing," Dr. Agrawal wrote.

The SF-SPQ was developed based on data collected from 1,153 pregnant women seen in three outpatient clinics between 2010 and 2013. Sleep patterns were assessed by the Berlin Questionnaire, Epworth Sleepiness Scale, and by questions regarding napping behavior. A confirmatory factor analysis (CFA) was performed to develop a sensitive and specific sleep scale derived from the findings. The scale ultimately included "snoring frequently," "bothersome snoring," "stopped breathing while sleeping," and "falling asleep while driving."

"These items were conceptually related to sleep-disordered breathing during pregnancy, statistically intercorrelated, and/or associated with adverse outcomes. CFA factor loadings were significant and model fit was good," Dr. Agrawal wrote.

In addition to higher score on the SF-SPQ, adjusted relative risks of adverse outcomes were associated with BMI greater than 30 (adjusted relative risk, 1.55), hypertension (adjusted RR, 5.07), and screening positive on the Berlin Questionnaire (adjusted RR, 2.45).

"These data suggest that comorbid conditions such as obesity and hypertension (which are themselves a part of the Berlin Questionnaire) drive association with pregnancy outcomes. However, preeclampsia was independently associated with the SF-SPQ," Dr. Agrawal noted.

Prior studies have demonstrated that sleep-disordered breathing during pregnancy is associated with adverse pregnancy outcomes, but an efficient and efficacious screening tool for sleep disorders has been lacking.

The findings are important, because in the United States, preeclampsia affects up to 6% of pregnancies and is linked with other morbidities such as intrauterine growth restriction, and because studies suggest that the use of continuous positive airway pressure (CPAP) can reduce the risk of preeclampsia in pregnant patients with sleep-disordered breathing.

Additional research is needed to evaluate the efficacy of the SF-SPQ for detecting women at risk, Dr. Agrawal concluded.

Dr. Agrawal reported having no disclosures.

DESTIN, FLA. – Facet joint osteoarthritis likely accounts for much of what is classified as "nonspecific" low back pain, according to Dr. Alfred C. Gellhorn.

"Amazingly – and I think sadly for us – the lumbar facet joints really have received very little attention in the literature," Dr. Gellhorn, who works in the department of rehabilitation medicine at the University of Washington, Seattle, said at the annual Congress of Clinical Rheumatology.

Eight of every ten American will experience low back pain at some point during their lifetime; low back pain is second only to the common cold in frequency, is the most common reason for time off work, and has a total social cost of more than $100 billion annually. Up to 85% of patients never receive a definitive diagnosis and are classified has having nonspecific pain, he said.

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The facet joints may be responsible for a significant proportion of that pain.

Facet joint cartilage is aneural, but a number of nociceptors exist in the subchondral bone, the synovial folds, and the capsule. Once activated – by synovial inflammation or mechanical factors such as trabecular microfractures, capsular distention, pressure on the subchondral bone as joint load increases, or intramedullary hypertension, for example – the nociceptors may cause secondary reflex contraction of paraspinal muscles.

Patients will report this as spasms, and the contractions can be palpated, Dr. Gellhorn said, noting that prolonged inflammation in and around the facet joints can lead to central sensitization, neuronal plasticity, and development of chronic low back pain.

Facet joint osteoarthritis (OA) is distinct from disc degeneration, but the two conditions are interdependent. Radiographic hallmarks of disc degeneration include disc height loss, dehydration, and endplate sclerosis, whereas radiographic hallmarks of facet joint OA include narrowing of the facet joint space, osteophytosis of articular processes, hypertrophy of articular processes, sclerosis, subchondral erosion, and subchondral cysts.

Older studies that looked at facet joint OA by comparing findings on imaging and symptoms found either no association or only minimal association between facet joint OA and low back pain, but the threshold used in those studies was mild to moderate OA in young and middle-aged subjects.

"That’s the wrong criterion to use," Dr. Gellhorn said, noting that mild facet joint OA is "essentially ubiquitous" by middle age. Moderate to severe facet OA, however, is more symptomatic, and predominantly affects older adults – and should be the criterion used in studies of the condition.

In a recent study of 252 patients with a mean age of 67 years who were participants in the Framingham heart study, severe OA affecting the facet joint was significantly associated with frequent low back pain (odds ratio, 2.2). Disc height narrowing was not associated with low back pain in these patients (Osteoarthritis Cartilage 2013;21:1199-206).

The findings contrast with those from prior studies, likely because the cohort was older (mean age of 67 years vs. 30s to 50s), he said.

It may be that with age, back pain classified as "nonspecific" shifts from discogenic pain in younger adults to facetogenic pain in older adults, he suggested.

Findings with respect to disc pathology and low back pain in young and middle-aged adults seem to support this hypothesis, he noted.

For example, in a study of patients with a mean age of 49 years, low back pain was associated with a twofold increased likelihood of disc height loss and annular tears, and in a study of patients aged 18-50 years, moderate disc height loss was also associated with a twofold increased likelihood of low back pain. In another study of patients with a mean age of 50 years, advanced disc height loss was associated with a threefold increased likelihood of prevalent low back pain.

In another study, severe disc height narrowing was associated with a threefold increase in the odds of low back pain in those younger than age 60 years but not in those over age 60 years.

There are markers for symptomatic facet joint OA. Despite the known association between severe facet joint OA and low back pain, "the truth is there is still limited positive predictive value for that," he said.

"Many older adults with severe facet joint OA on imaging are relatively asymptomatic," he added.

There are some additional imaging makers, however. Symptomatic facet join OA is apparent on single-photon emission computed tomography/computed tomography (SPECT/CT) or fluid-sensitive, fat-suppressed MRI. Also, 64% of patients with suspected facet joint pain in one study had bone marrow lesions on short T1 inversion recovery (STIR) MRI, which were well correlated to the side of pain, he said.

There are no serum biomarkers for the condition at present, he noted.

In addition to older age and these findings on imaging, other risk factors and correlates for facet joint OA include sex (women are 1.5-1.9 times more likely than men to have facet joint OA), race (African Americans are about 60% less likely than white Americans to have facet joint OA), and high body mass index (those with BMI of 25-30 and 30-35 have a three- and fivefold increased risk of lumbar pain associated with facet joint OA, respectively, compared with those with BMI below 25).

Abdominal aortic calcifications and more sagittal orientation of the joints (vs. coronal orientation), also are associated with facet joint OA, Dr. Gellhorn said.

With additional research, these factors could be useful for "disambiguating nonspecific low back pain," he said.

"I think we’re getting closer. We’re not there yet, but we’re getting closer," he said.

Clinically, facet joint OA often presents as localized back or neck pain at C5-C6 with some radiation into the scapular region.

"It’s less clear in the lumbar spine, but almost always people will have pain in the lumbar region, and almost always they will have pain that radiates into the buttocks," he said, noting that pain radiating into the anterior or lateral thighs can be associated with facet joint OA, but pain that extends below the knees is more likely to be radicular.

There are no specific examination maneuvers that are pathognomonic – or even particularly helpful – for the condition, he added.

It is important to keep in mind that many patients will have associated conditions, including spondylolisthesis, disc degeneration, scoliosis, muscle atrophy, and spinal stenosis.

"It’s easy to get overwhelmed in the face of this, but I would urge you not to, and to still try to disentangle some of these concepts of low back pain without throwing up your hands," he said.

Although anesthetic blockade of the medial branches of the dorsal primary ramus (or "medial branch blocks,") are considered the gold standard for diagnosis, they are controversial, have an unacceptably high rate of false-positive results with a single block, and thus may require comparative blocks, which can result in numerous spinal injections.

This is problematic; there is no good way to make the diagnosis before doing more rational, conservative treatment, he said.

"I think that there are probably better things than doing 30 injections into someone’s spine to establish a diagnosis," he said.

In fact, treatment for facet joint OA generally involves physical activity.

"You don’t want to push these people to their limits, but certainly it is important to have them move and to have them keep the strength in their spine," he said.

In the absence of good studies evaluating noninterventional therapy for confirmed facet joint pain, treatment is generally based on findings in patients with chronic nonspecific low back pain and knee OA, and there is evidence in both of those settings that suggest exercise is helpful for increasing strength and decreasing pain and disability.

A Cochrane review showed that exercise therapy provides mild to moderate benefit. Additional studies have suggested that early referral to physical therapy results in modest improvement in function at 12 months in older adults, suggesting physical therapy provides longer-term results than many other interventions for low back pain, which tend to provide only short-term relief, he noted.

Furthermore, patients who have physical therapy tend to require fewer interventions. Dr. Gellhorn found in a recent study that physical therapy in a Medicare population with low back pain was associated with fewer lumbar injections, physician office visits, and lumbar surgeries.

"So it’s very reasonable to send your patients with facet joint OA to PT," he said.

Other treatments that may have some benefit if physical activity is inadequate include intra-articular steroid injections and radiofrequency denervation.

In studies that used SPECT for inclusion criteria, intra-articular injections were better than medial branch blocks at 3 months, and were more effective at 1 month and 3 months than were injections used in studies that did not use SPECT for inclusion, he said.

Injections were not useful in studies that used physical examination or diagnostic block for inclusion.

"So if you’re basing it on metabolic activity, you’re likely to have a good outcome from your injection," he said.

Radiofrequency denervation tends to work better in the cervical spine than in the lumbar spine, but it is difficult to justify in practice because it requires medial branch block, or double or even triple block to optimize success, and because it is associated with a number of potential complications, such as loss of innervation to the multifidus muscles.

In his practice he first screens for red flags in patients who present with low back pain. Next, he gets an X-ray to look for alignment issues, and he "heavily considers – if the clinical picture fits" – whether facet joint OA might be the cause of the pain.

"I’ll talk to them about it, and then almost always, I’ll send them for an empiric trial of physical therapy plus or minus some analgesics – Tylenol or NSAIDs," he said.

If patients experience improved function and a decrease in symptoms within 6-8 weeks, he recommends that they begin a more interesting (than their home physical therapy regimen) exercise program, such as yoga or Pilates to help them maintain those gains; if they remain symptomatic, he images them.

He starts with SPECT/CT rather than MRI if facet joint OA is high on his differential list for the patient, and if that’s positive, he will consider intra-articular steroid injections. If the injections are effective he recommends yoga and/or Pilates for maintaining the gains.

In rare cases a patient doesn’t respond to the injections, and then he will consider more aggressive treatment, such as medial branch block or radiofrequency denervation.

Understanding of facet joint OA has been slow to emerge, but progress is being made, Dr. Gellhorn said.

For example, the work with SPECT/CT and STIR MRI is very exciting, he said.

"I think this is going to give us a number of things to work with: first and foremost, it’s going to give us better criteria to diagnose patients and enroll them in treatment studies," he said.

Serum, urine, and genetic biomarkers, on the other hand, are interesting and on the horizon, "but we’re not really there yet," he added.

"But I think we will be able to at least use imaging studies to monitor some response to treatment," he said.

Additional study is also needed with respect to conservative treatments. Studies comparing different exercise programs, including studies comparing strength vs. flexibility and extension vs. flexion, are needed.

Regenerative treatments, such as platelet rich plasma and autologous stem cells are another area of interest, he said.

Dr. Gellhorn reported having no disclosures.

DESTIN, FLA. – Facet joint osteoarthritis likely accounts for much of what is classified as "nonspecific" low back pain, according to Dr. Alfred C. Gellhorn.

"Amazingly – and I think sadly for us – the lumbar facet joints really have received very little attention in the literature," Dr. Gellhorn, who works in the department of rehabilitation medicine at the University of Washington, Seattle, said at the annual Congress of Clinical Rheumatology.

Eight of every ten American will experience low back pain at some point during their lifetime; low back pain is second only to the common cold in frequency, is the most common reason for time off work, and has a total social cost of more than $100 billion annually. Up to 85% of patients never receive a definitive diagnosis and are classified has having nonspecific pain, he said.

©Rocky89/thinkstockphotos.com

The facet joints may be responsible for a significant proportion of that pain.

Facet joint cartilage is aneural, but a number of nociceptors exist in the subchondral bone, the synovial folds, and the capsule. Once activated – by synovial inflammation or mechanical factors such as trabecular microfractures, capsular distention, pressure on the subchondral bone as joint load increases, or intramedullary hypertension, for example – the nociceptors may cause secondary reflex contraction of paraspinal muscles.

Patients will report this as spasms, and the contractions can be palpated, Dr. Gellhorn said, noting that prolonged inflammation in and around the facet joints can lead to central sensitization, neuronal plasticity, and development of chronic low back pain.

Facet joint osteoarthritis (OA) is distinct from disc degeneration, but the two conditions are interdependent. Radiographic hallmarks of disc degeneration include disc height loss, dehydration, and endplate sclerosis, whereas radiographic hallmarks of facet joint OA include narrowing of the facet joint space, osteophytosis of articular processes, hypertrophy of articular processes, sclerosis, subchondral erosion, and subchondral cysts.

Older studies that looked at facet joint OA by comparing findings on imaging and symptoms found either no association or only minimal association between facet joint OA and low back pain, but the threshold used in those studies was mild to moderate OA in young and middle-aged subjects.

"That’s the wrong criterion to use," Dr. Gellhorn said, noting that mild facet joint OA is "essentially ubiquitous" by middle age. Moderate to severe facet OA, however, is more symptomatic, and predominantly affects older adults – and should be the criterion used in studies of the condition.

In a recent study of 252 patients with a mean age of 67 years who were participants in the Framingham heart study, severe OA affecting the facet joint was significantly associated with frequent low back pain (odds ratio, 2.2). Disc height narrowing was not associated with low back pain in these patients (Osteoarthritis Cartilage 2013;21:1199-206).

The findings contrast with those from prior studies, likely because the cohort was older (mean age of 67 years vs. 30s to 50s), he said.

It may be that with age, back pain classified as "nonspecific" shifts from discogenic pain in younger adults to facetogenic pain in older adults, he suggested.

Findings with respect to disc pathology and low back pain in young and middle-aged adults seem to support this hypothesis, he noted.

For example, in a study of patients with a mean age of 49 years, low back pain was associated with a twofold increased likelihood of disc height loss and annular tears, and in a study of patients aged 18-50 years, moderate disc height loss was also associated with a twofold increased likelihood of low back pain. In another study of patients with a mean age of 50 years, advanced disc height loss was associated with a threefold increased likelihood of prevalent low back pain.

In another study, severe disc height narrowing was associated with a threefold increase in the odds of low back pain in those younger than age 60 years but not in those over age 60 years.

There are markers for symptomatic facet joint OA. Despite the known association between severe facet joint OA and low back pain, "the truth is there is still limited positive predictive value for that," he said.

"Many older adults with severe facet joint OA on imaging are relatively asymptomatic," he added.

There are some additional imaging makers, however. Symptomatic facet join OA is apparent on single-photon emission computed tomography/computed tomography (SPECT/CT) or fluid-sensitive, fat-suppressed MRI. Also, 64% of patients with suspected facet joint pain in one study had bone marrow lesions on short T1 inversion recovery (STIR) MRI, which were well correlated to the side of pain, he said.

There are no serum biomarkers for the condition at present, he noted.

In addition to older age and these findings on imaging, other risk factors and correlates for facet joint OA include sex (women are 1.5-1.9 times more likely than men to have facet joint OA), race (African Americans are about 60% less likely than white Americans to have facet joint OA), and high body mass index (those with BMI of 25-30 and 30-35 have a three- and fivefold increased risk of lumbar pain associated with facet joint OA, respectively, compared with those with BMI below 25).

Abdominal aortic calcifications and more sagittal orientation of the joints (vs. coronal orientation), also are associated with facet joint OA, Dr. Gellhorn said.

With additional research, these factors could be useful for "disambiguating nonspecific low back pain," he said.

"I think we’re getting closer. We’re not there yet, but we’re getting closer," he said.

Clinically, facet joint OA often presents as localized back or neck pain at C5-C6 with some radiation into the scapular region.

"It’s less clear in the lumbar spine, but almost always people will have pain in the lumbar region, and almost always they will have pain that radiates into the buttocks," he said, noting that pain radiating into the anterior or lateral thighs can be associated with facet joint OA, but pain that extends below the knees is more likely to be radicular.

There are no specific examination maneuvers that are pathognomonic – or even particularly helpful – for the condition, he added.

It is important to keep in mind that many patients will have associated conditions, including spondylolisthesis, disc degeneration, scoliosis, muscle atrophy, and spinal stenosis.

"It’s easy to get overwhelmed in the face of this, but I would urge you not to, and to still try to disentangle some of these concepts of low back pain without throwing up your hands," he said.

Although anesthetic blockade of the medial branches of the dorsal primary ramus (or "medial branch blocks,") are considered the gold standard for diagnosis, they are controversial, have an unacceptably high rate of false-positive results with a single block, and thus may require comparative blocks, which can result in numerous spinal injections.

This is problematic; there is no good way to make the diagnosis before doing more rational, conservative treatment, he said.

"I think that there are probably better things than doing 30 injections into someone’s spine to establish a diagnosis," he said.

In fact, treatment for facet joint OA generally involves physical activity.

"You don’t want to push these people to their limits, but certainly it is important to have them move and to have them keep the strength in their spine," he said.

In the absence of good studies evaluating noninterventional therapy for confirmed facet joint pain, treatment is generally based on findings in patients with chronic nonspecific low back pain and knee OA, and there is evidence in both of those settings that suggest exercise is helpful for increasing strength and decreasing pain and disability.

A Cochrane review showed that exercise therapy provides mild to moderate benefit. Additional studies have suggested that early referral to physical therapy results in modest improvement in function at 12 months in older adults, suggesting physical therapy provides longer-term results than many other interventions for low back pain, which tend to provide only short-term relief, he noted.

Furthermore, patients who have physical therapy tend to require fewer interventions. Dr. Gellhorn found in a recent study that physical therapy in a Medicare population with low back pain was associated with fewer lumbar injections, physician office visits, and lumbar surgeries.

"So it’s very reasonable to send your patients with facet joint OA to PT," he said.

Other treatments that may have some benefit if physical activity is inadequate include intra-articular steroid injections and radiofrequency denervation.

In studies that used SPECT for inclusion criteria, intra-articular injections were better than medial branch blocks at 3 months, and were more effective at 1 month and 3 months than were injections used in studies that did not use SPECT for inclusion, he said.

Injections were not useful in studies that used physical examination or diagnostic block for inclusion.

"So if you’re basing it on metabolic activity, you’re likely to have a good outcome from your injection," he said.

Radiofrequency denervation tends to work better in the cervical spine than in the lumbar spine, but it is difficult to justify in practice because it requires medial branch block, or double or even triple block to optimize success, and because it is associated with a number of potential complications, such as loss of innervation to the multifidus muscles.

In his practice he first screens for red flags in patients who present with low back pain. Next, he gets an X-ray to look for alignment issues, and he "heavily considers – if the clinical picture fits" – whether facet joint OA might be the cause of the pain.

"I’ll talk to them about it, and then almost always, I’ll send them for an empiric trial of physical therapy plus or minus some analgesics – Tylenol or NSAIDs," he said.

If patients experience improved function and a decrease in symptoms within 6-8 weeks, he recommends that they begin a more interesting (than their home physical therapy regimen) exercise program, such as yoga or Pilates to help them maintain those gains; if they remain symptomatic, he images them.

He starts with SPECT/CT rather than MRI if facet joint OA is high on his differential list for the patient, and if that’s positive, he will consider intra-articular steroid injections. If the injections are effective he recommends yoga and/or Pilates for maintaining the gains.

In rare cases a patient doesn’t respond to the injections, and then he will consider more aggressive treatment, such as medial branch block or radiofrequency denervation.

Understanding of facet joint OA has been slow to emerge, but progress is being made, Dr. Gellhorn said.

For example, the work with SPECT/CT and STIR MRI is very exciting, he said.

"I think this is going to give us a number of things to work with: first and foremost, it’s going to give us better criteria to diagnose patients and enroll them in treatment studies," he said.

Serum, urine, and genetic biomarkers, on the other hand, are interesting and on the horizon, "but we’re not really there yet," he added.

"But I think we will be able to at least use imaging studies to monitor some response to treatment," he said.

Additional study is also needed with respect to conservative treatments. Studies comparing different exercise programs, including studies comparing strength vs. flexibility and extension vs. flexion, are needed.

Regenerative treatments, such as platelet rich plasma and autologous stem cells are another area of interest, he said.

Dr. Gellhorn reported having no disclosures.

DESTIN, FLA. – Facet joint osteoarthritis likely accounts for much of what is classified as "nonspecific" low back pain, according to Dr. Alfred C. Gellhorn.

"Amazingly – and I think sadly for us – the lumbar facet joints really have received very little attention in the literature," Dr. Gellhorn, who works in the department of rehabilitation medicine at the University of Washington, Seattle, said at the annual Congress of Clinical Rheumatology.

Eight of every ten American will experience low back pain at some point during their lifetime; low back pain is second only to the common cold in frequency, is the most common reason for time off work, and has a total social cost of more than $100 billion annually. Up to 85% of patients never receive a definitive diagnosis and are classified has having nonspecific pain, he said.

©Rocky89/thinkstockphotos.com

The facet joints may be responsible for a significant proportion of that pain.

Facet joint cartilage is aneural, but a number of nociceptors exist in the subchondral bone, the synovial folds, and the capsule. Once activated – by synovial inflammation or mechanical factors such as trabecular microfractures, capsular distention, pressure on the subchondral bone as joint load increases, or intramedullary hypertension, for example – the nociceptors may cause secondary reflex contraction of paraspinal muscles.

Patients will report this as spasms, and the contractions can be palpated, Dr. Gellhorn said, noting that prolonged inflammation in and around the facet joints can lead to central sensitization, neuronal plasticity, and development of chronic low back pain.

Facet joint osteoarthritis (OA) is distinct from disc degeneration, but the two conditions are interdependent. Radiographic hallmarks of disc degeneration include disc height loss, dehydration, and endplate sclerosis, whereas radiographic hallmarks of facet joint OA include narrowing of the facet joint space, osteophytosis of articular processes, hypertrophy of articular processes, sclerosis, subchondral erosion, and subchondral cysts.

Older studies that looked at facet joint OA by comparing findings on imaging and symptoms found either no association or only minimal association between facet joint OA and low back pain, but the threshold used in those studies was mild to moderate OA in young and middle-aged subjects.

"That’s the wrong criterion to use," Dr. Gellhorn said, noting that mild facet joint OA is "essentially ubiquitous" by middle age. Moderate to severe facet OA, however, is more symptomatic, and predominantly affects older adults – and should be the criterion used in studies of the condition.

In a recent study of 252 patients with a mean age of 67 years who were participants in the Framingham heart study, severe OA affecting the facet joint was significantly associated with frequent low back pain (odds ratio, 2.2). Disc height narrowing was not associated with low back pain in these patients (Osteoarthritis Cartilage 2013;21:1199-206).

The findings contrast with those from prior studies, likely because the cohort was older (mean age of 67 years vs. 30s to 50s), he said.

It may be that with age, back pain classified as "nonspecific" shifts from discogenic pain in younger adults to facetogenic pain in older adults, he suggested.

Findings with respect to disc pathology and low back pain in young and middle-aged adults seem to support this hypothesis, he noted.

For example, in a study of patients with a mean age of 49 years, low back pain was associated with a twofold increased likelihood of disc height loss and annular tears, and in a study of patients aged 18-50 years, moderate disc height loss was also associated with a twofold increased likelihood of low back pain. In another study of patients with a mean age of 50 years, advanced disc height loss was associated with a threefold increased likelihood of prevalent low back pain.

In another study, severe disc height narrowing was associated with a threefold increase in the odds of low back pain in those younger than age 60 years but not in those over age 60 years.

There are markers for symptomatic facet joint OA. Despite the known association between severe facet joint OA and low back pain, "the truth is there is still limited positive predictive value for that," he said.

"Many older adults with severe facet joint OA on imaging are relatively asymptomatic," he added.

There are some additional imaging makers, however. Symptomatic facet join OA is apparent on single-photon emission computed tomography/computed tomography (SPECT/CT) or fluid-sensitive, fat-suppressed MRI. Also, 64% of patients with suspected facet joint pain in one study had bone marrow lesions on short T1 inversion recovery (STIR) MRI, which were well correlated to the side of pain, he said.

There are no serum biomarkers for the condition at present, he noted.

In addition to older age and these findings on imaging, other risk factors and correlates for facet joint OA include sex (women are 1.5-1.9 times more likely than men to have facet joint OA), race (African Americans are about 60% less likely than white Americans to have facet joint OA), and high body mass index (those with BMI of 25-30 and 30-35 have a three- and fivefold increased risk of lumbar pain associated with facet joint OA, respectively, compared with those with BMI below 25).

Abdominal aortic calcifications and more sagittal orientation of the joints (vs. coronal orientation), also are associated with facet joint OA, Dr. Gellhorn said.

With additional research, these factors could be useful for "disambiguating nonspecific low back pain," he said.

"I think we’re getting closer. We’re not there yet, but we’re getting closer," he said.

Clinically, facet joint OA often presents as localized back or neck pain at C5-C6 with some radiation into the scapular region.

"It’s less clear in the lumbar spine, but almost always people will have pain in the lumbar region, and almost always they will have pain that radiates into the buttocks," he said, noting that pain radiating into the anterior or lateral thighs can be associated with facet joint OA, but pain that extends below the knees is more likely to be radicular.

There are no specific examination maneuvers that are pathognomonic – or even particularly helpful – for the condition, he added.

It is important to keep in mind that many patients will have associated conditions, including spondylolisthesis, disc degeneration, scoliosis, muscle atrophy, and spinal stenosis.

"It’s easy to get overwhelmed in the face of this, but I would urge you not to, and to still try to disentangle some of these concepts of low back pain without throwing up your hands," he said.

Although anesthetic blockade of the medial branches of the dorsal primary ramus (or "medial branch blocks,") are considered the gold standard for diagnosis, they are controversial, have an unacceptably high rate of false-positive results with a single block, and thus may require comparative blocks, which can result in numerous spinal injections.

This is problematic; there is no good way to make the diagnosis before doing more rational, conservative treatment, he said.

"I think that there are probably better things than doing 30 injections into someone’s spine to establish a diagnosis," he said.

In fact, treatment for facet joint OA generally involves physical activity.

"You don’t want to push these people to their limits, but certainly it is important to have them move and to have them keep the strength in their spine," he said.

In the absence of good studies evaluating noninterventional therapy for confirmed facet joint pain, treatment is generally based on findings in patients with chronic nonspecific low back pain and knee OA, and there is evidence in both of those settings that suggest exercise is helpful for increasing strength and decreasing pain and disability.

A Cochrane review showed that exercise therapy provides mild to moderate benefit. Additional studies have suggested that early referral to physical therapy results in modest improvement in function at 12 months in older adults, suggesting physical therapy provides longer-term results than many other interventions for low back pain, which tend to provide only short-term relief, he noted.

Furthermore, patients who have physical therapy tend to require fewer interventions. Dr. Gellhorn found in a recent study that physical therapy in a Medicare population with low back pain was associated with fewer lumbar injections, physician office visits, and lumbar surgeries.

"So it’s very reasonable to send your patients with facet joint OA to PT," he said.

Other treatments that may have some benefit if physical activity is inadequate include intra-articular steroid injections and radiofrequency denervation.

In studies that used SPECT for inclusion criteria, intra-articular injections were better than medial branch blocks at 3 months, and were more effective at 1 month and 3 months than were injections used in studies that did not use SPECT for inclusion, he said.

Injections were not useful in studies that used physical examination or diagnostic block for inclusion.

"So if you’re basing it on metabolic activity, you’re likely to have a good outcome from your injection," he said.

Radiofrequency denervation tends to work better in the cervical spine than in the lumbar spine, but it is difficult to justify in practice because it requires medial branch block, or double or even triple block to optimize success, and because it is associated with a number of potential complications, such as loss of innervation to the multifidus muscles.

In his practice he first screens for red flags in patients who present with low back pain. Next, he gets an X-ray to look for alignment issues, and he "heavily considers – if the clinical picture fits" – whether facet joint OA might be the cause of the pain.

"I’ll talk to them about it, and then almost always, I’ll send them for an empiric trial of physical therapy plus or minus some analgesics – Tylenol or NSAIDs," he said.

If patients experience improved function and a decrease in symptoms within 6-8 weeks, he recommends that they begin a more interesting (than their home physical therapy regimen) exercise program, such as yoga or Pilates to help them maintain those gains; if they remain symptomatic, he images them.

He starts with SPECT/CT rather than MRI if facet joint OA is high on his differential list for the patient, and if that’s positive, he will consider intra-articular steroid injections. If the injections are effective he recommends yoga and/or Pilates for maintaining the gains.

In rare cases a patient doesn’t respond to the injections, and then he will consider more aggressive treatment, such as medial branch block or radiofrequency denervation.

Understanding of facet joint OA has been slow to emerge, but progress is being made, Dr. Gellhorn said.

For example, the work with SPECT/CT and STIR MRI is very exciting, he said.

"I think this is going to give us a number of things to work with: first and foremost, it’s going to give us better criteria to diagnose patients and enroll them in treatment studies," he said.

Serum, urine, and genetic biomarkers, on the other hand, are interesting and on the horizon, "but we’re not really there yet," he added.

"But I think we will be able to at least use imaging studies to monitor some response to treatment," he said.

Additional study is also needed with respect to conservative treatments. Studies comparing different exercise programs, including studies comparing strength vs. flexibility and extension vs. flexion, are needed.

Regenerative treatments, such as platelet rich plasma and autologous stem cells are another area of interest, he said.

Dr. Gellhorn reported having no disclosures.

DESTIN, FLA. – Personalized medicine – picking the right patient for the right drug – is a hot topic in medicine in general, but the approach is challenging for rheumatoid arthritis because of its heterogeneity, according to Dr. Arthur Kavanaugh.

"How do we get to personalized medicine? Do we have a biomarker for any of our treatments? Well, ‘biomarker’ is sort of a generic term. We actually don’t want a biomarker – anything is a biomarker. What we want are surrogate markers. We want something that is so strong, that we can measure that and predict what’s going to happen," Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

He used the example of CD4 count in HIV infection and dual-energy x-ray absorptiometry scans for fragility fractures as useful surrogate markers.

"Some people would say ‘cholesterol for atherosclerotic disease.’ Well, you don’t care about the cholesterol – you care about whether you’re going to have a heart attack. So a surrogate marker is a much higher standard," he explained.

In rheumatology, there is a lack of such surrogate markers.

"We have lots of biomarkers, but there’s really nothing that’s a surrogate marker in rheumatology that will allow us to pick one treatment over another. It’s something we would love to see, and it’s been looked at in a number of ways," he said.

For example, the genomic approach was expected to be the answer.

"For those of us who were around before the human genome was sequenced – that was going to be the answer. Go to the doctor, swab your cheek, turn that in to the nurse, walk out with a prescription based on your genes – that was going to be it. It hasn’t worked out that way; humans are complicated," he said.

Proteomics, glycomics, immunomics – all kinds of things have been looked at, Dr. Kavanaugh pointed out.

For awhile, geneticists were promising that if they could just get enough samples, they would be able to figure out which patients should get which drug.

"Well, they kind of failed, and now I think a very interesting article that just came out in Nature is just sort of them surrendering and saying, ‘OK, what we’ve done now is take the treatments you know work, and we will figure out which genes predict that,’" he said.

The paper is a meta-analysis of genome-wide association studies, and it looks at how RA genetics can contribute to drug discovery (Nature 2014;506: 376-81).

The authors found about 100 loci that seemed to be informative, Dr. Kavanaugh said. "It’s very interesting, because ... a lot of the loci map to therapies that we have now."

So maybe this backwards "bedside-to-bench" approach will prove useful for providing more personalized medicine.

Epigenetics might also have promise for advancing personalized medicine for RA.

"It’s fascinating. We don’t know so much about it, but of course they are heritable alterations that don’t change the DNA sequence," he said.

Examples include DNA methylation, micro-RNAs, which affect the expression of genes, and histone modification.

These can be inherited, and while the concept opens up some politically charged and socioeconomic issues with respect to how epigenetic modifications might affect an individual, it’s an area that may have some relevance in personalized medicine, Dr. Kavanaugh said.

In some ways, the progress with personalized medicine in RA has been hampered by the results in other fields.

"There’s been so much progress in oncology, but they have more monogenic disease," he said, explaining that a single abnormality can predict whether a drug will work in 0% or 80% of cases. "That’s personalized medicine, but I don’t think we have that for rheumatic disease. It would be great if we did, but I don’t think we’re there yet."

In the rheumatic diseases, it may be that things have to be considered in a different, more complex way, by using combinations of biomarkers, for example.

In a poster presented at EULAR in 2013, based on the ADACTA study, he and his colleagues reported that none of a number of single biomarkers predicted response, but that patterns of biomarkers – in this case serum markers that correlated with immunologic phenotypes in the synovium from previous studies – appeared to have predictive value.

"Of course, this is predicting the past ... we have to see if this kind of stuff holds up. We would all love to have it. This is the next challenge – using it in a more rational way so that we can get our patients to the best possible place," he said.

Dr. Kavanaugh reported having no relevant financial disclosures.

DESTIN, FLA. – Personalized medicine – picking the right patient for the right drug – is a hot topic in medicine in general, but the approach is challenging for rheumatoid arthritis because of its heterogeneity, according to Dr. Arthur Kavanaugh.

"How do we get to personalized medicine? Do we have a biomarker for any of our treatments? Well, ‘biomarker’ is sort of a generic term. We actually don’t want a biomarker – anything is a biomarker. What we want are surrogate markers. We want something that is so strong, that we can measure that and predict what’s going to happen," Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

He used the example of CD4 count in HIV infection and dual-energy x-ray absorptiometry scans for fragility fractures as useful surrogate markers.

"Some people would say ‘cholesterol for atherosclerotic disease.’ Well, you don’t care about the cholesterol – you care about whether you’re going to have a heart attack. So a surrogate marker is a much higher standard," he explained.

In rheumatology, there is a lack of such surrogate markers.

"We have lots of biomarkers, but there’s really nothing that’s a surrogate marker in rheumatology that will allow us to pick one treatment over another. It’s something we would love to see, and it’s been looked at in a number of ways," he said.

For example, the genomic approach was expected to be the answer.

"For those of us who were around before the human genome was sequenced – that was going to be the answer. Go to the doctor, swab your cheek, turn that in to the nurse, walk out with a prescription based on your genes – that was going to be it. It hasn’t worked out that way; humans are complicated," he said.

Proteomics, glycomics, immunomics – all kinds of things have been looked at, Dr. Kavanaugh pointed out.

For awhile, geneticists were promising that if they could just get enough samples, they would be able to figure out which patients should get which drug.

"Well, they kind of failed, and now I think a very interesting article that just came out in Nature is just sort of them surrendering and saying, ‘OK, what we’ve done now is take the treatments you know work, and we will figure out which genes predict that,’" he said.

The paper is a meta-analysis of genome-wide association studies, and it looks at how RA genetics can contribute to drug discovery (Nature 2014;506: 376-81).

The authors found about 100 loci that seemed to be informative, Dr. Kavanaugh said. "It’s very interesting, because ... a lot of the loci map to therapies that we have now."

So maybe this backwards "bedside-to-bench" approach will prove useful for providing more personalized medicine.

Epigenetics might also have promise for advancing personalized medicine for RA.

"It’s fascinating. We don’t know so much about it, but of course they are heritable alterations that don’t change the DNA sequence," he said.

Examples include DNA methylation, micro-RNAs, which affect the expression of genes, and histone modification.

These can be inherited, and while the concept opens up some politically charged and socioeconomic issues with respect to how epigenetic modifications might affect an individual, it’s an area that may have some relevance in personalized medicine, Dr. Kavanaugh said.

In some ways, the progress with personalized medicine in RA has been hampered by the results in other fields.

"There’s been so much progress in oncology, but they have more monogenic disease," he said, explaining that a single abnormality can predict whether a drug will work in 0% or 80% of cases. "That’s personalized medicine, but I don’t think we have that for rheumatic disease. It would be great if we did, but I don’t think we’re there yet."

In the rheumatic diseases, it may be that things have to be considered in a different, more complex way, by using combinations of biomarkers, for example.

In a poster presented at EULAR in 2013, based on the ADACTA study, he and his colleagues reported that none of a number of single biomarkers predicted response, but that patterns of biomarkers – in this case serum markers that correlated with immunologic phenotypes in the synovium from previous studies – appeared to have predictive value.

"Of course, this is predicting the past ... we have to see if this kind of stuff holds up. We would all love to have it. This is the next challenge – using it in a more rational way so that we can get our patients to the best possible place," he said.

Dr. Kavanaugh reported having no relevant financial disclosures.

DESTIN, FLA. – Personalized medicine – picking the right patient for the right drug – is a hot topic in medicine in general, but the approach is challenging for rheumatoid arthritis because of its heterogeneity, according to Dr. Arthur Kavanaugh.

"How do we get to personalized medicine? Do we have a biomarker for any of our treatments? Well, ‘biomarker’ is sort of a generic term. We actually don’t want a biomarker – anything is a biomarker. What we want are surrogate markers. We want something that is so strong, that we can measure that and predict what’s going to happen," Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, said at the annual Congress of Clinical Rheumatology.

He used the example of CD4 count in HIV infection and dual-energy x-ray absorptiometry scans for fragility fractures as useful surrogate markers.

"Some people would say ‘cholesterol for atherosclerotic disease.’ Well, you don’t care about the cholesterol – you care about whether you’re going to have a heart attack. So a surrogate marker is a much higher standard," he explained.

In rheumatology, there is a lack of such surrogate markers.

"We have lots of biomarkers, but there’s really nothing that’s a surrogate marker in rheumatology that will allow us to pick one treatment over another. It’s something we would love to see, and it’s been looked at in a number of ways," he said.

For example, the genomic approach was expected to be the answer.

"For those of us who were around before the human genome was sequenced – that was going to be the answer. Go to the doctor, swab your cheek, turn that in to the nurse, walk out with a prescription based on your genes – that was going to be it. It hasn’t worked out that way; humans are complicated," he said.

Proteomics, glycomics, immunomics – all kinds of things have been looked at, Dr. Kavanaugh pointed out.

For awhile, geneticists were promising that if they could just get enough samples, they would be able to figure out which patients should get which drug.

"Well, they kind of failed, and now I think a very interesting article that just came out in Nature is just sort of them surrendering and saying, ‘OK, what we’ve done now is take the treatments you know work, and we will figure out which genes predict that,’" he said.

The paper is a meta-analysis of genome-wide association studies, and it looks at how RA genetics can contribute to drug discovery (Nature 2014;506: 376-81).

The authors found about 100 loci that seemed to be informative, Dr. Kavanaugh said. "It’s very interesting, because ... a lot of the loci map to therapies that we have now."

So maybe this backwards "bedside-to-bench" approach will prove useful for providing more personalized medicine.

Epigenetics might also have promise for advancing personalized medicine for RA.

"It’s fascinating. We don’t know so much about it, but of course they are heritable alterations that don’t change the DNA sequence," he said.

Examples include DNA methylation, micro-RNAs, which affect the expression of genes, and histone modification.

These can be inherited, and while the concept opens up some politically charged and socioeconomic issues with respect to how epigenetic modifications might affect an individual, it’s an area that may have some relevance in personalized medicine, Dr. Kavanaugh said.

In some ways, the progress with personalized medicine in RA has been hampered by the results in other fields.

"There’s been so much progress in oncology, but they have more monogenic disease," he said, explaining that a single abnormality can predict whether a drug will work in 0% or 80% of cases. "That’s personalized medicine, but I don’t think we have that for rheumatic disease. It would be great if we did, but I don’t think we’re there yet."

In the rheumatic diseases, it may be that things have to be considered in a different, more complex way, by using combinations of biomarkers, for example.

In a poster presented at EULAR in 2013, based on the ADACTA study, he and his colleagues reported that none of a number of single biomarkers predicted response, but that patterns of biomarkers – in this case serum markers that correlated with immunologic phenotypes in the synovium from previous studies – appeared to have predictive value.

"Of course, this is predicting the past ... we have to see if this kind of stuff holds up. We would all love to have it. This is the next challenge – using it in a more rational way so that we can get our patients to the best possible place," he said.

Dr. Kavanaugh reported having no relevant financial disclosures.

ORLANDO – A four kallikrein assay panel of human kallikrein and total, free, and intact prostate-specific antigen combined in an algorithm with age, digital rectal examination, and prior biopsy status provides a very high degree of discrimination for prostate cancer, compared with a PSA-based clinical algorithm, according to Dr. Daniel Lin.

The test (4Kscore test) was adapted from European studies which demonstrated that it is an accurate predictor of biopsy results, particularly for Gleason score 7 or greater disease, Dr. Lin of the University of Washington Medical Center, Seattle, reported during a late-breaking abstract session at the annual meeting of the American Urological Association.

In a prospective, blinded study, calibration of the 4Kscore algorithm in the first 300 patients enrolled from October 2013 to January 2014 was nearly perfect, compared with the European version, showing that the score works on an individual level, he said.

At one illustrative cut point, the score would have reduced the number of biopsies by 41%, with a negative-predictive value of 97%.

The test is of value at the population level, as well.

For high-grade disease, the 4Kscore test had a "very high and very robust" area under the curve of 0.82.

"The best comparator might be the [Prostate Cancer Prevention Trial] risk calculator, which takes into account age, PSA, Gleason grade, race, prior biopsy status, and the rectal examination," Dr. Lin said, explaining that findings with the two scores were "clearly nonoverlapping."

Even in the high-grade disease with a PSA of 2-10 in the "diagnostic gray zone," the 4Kscore test showed superiority for discrimination of high-grade disease.

A decision analysis demonstrated that clinical decision-making would be improved by the use of the 4Kscore test, he said.

Study subjects were 1,300 men scheduled for biopsy at any of 26 U.S. urology centers. Following phlebotomy, participants underwent at least a 10-core transrectal ultrasound-guided biopsy. The first 300 patients represented a calibration cohort, and the remaining 1,000 are part of a validation cohort.

The findings are of note, because controversy exists with respect to the use of PSA screening.

"We all know there are several challenges surrounding the early detection of prostate cancer, and particularly screening with PSA," Dr. Lin said, noting that positive screens lead to unnecessary biopsies.

In fact, about 60% of initial biopsies are negative, and about half of those that are positive are low-grade, potentially indolent disease, he said.

This, along with the fact that biopsies can be associated with complications and patient anxiety, has led to a negative perception of PSA screening among some medical organizations such as the U.S. Preventive Services Task Force, which has recommended against PSA screening of healthy men, despite evidence that PSA screening reduces mortality, Dr. Lin said.

Furthermore, treatment of low-risk disease is controversial, and data suggest that active surveillance is an acceptable strategy.

"Conversely, the treatment of intermediate- and high-risk disease has been supported by randomized, controlled trials, and there is a survival benefit for those men with intermediate- or high-risk disease," he said, noting that this underscores the importance of detecting high-grade disease.

The 4Kscore test addresses the controversies surrounding PSA screening and will address the concerns of policy makers who question prostate screening in general.

"The 4Kscore test yields superior performance to a clinical model based on the reduction of unnecessary biopsies and minimization of delay in diagnosing high-grade disease. The 4Kscore test is optimized for clinically relevant and actionable high-grade disease and can inform our decision making between the physician and patient, allowing for a unique personalization of risk. This will allow us to focus our efforts on treatment and evidence surrounding high-grade disease, which is clinically relevant," he concluded.

Funding for this study was provided by OPKO Diagnostics.

ORLANDO – A four kallikrein assay panel of human kallikrein and total, free, and intact prostate-specific antigen combined in an algorithm with age, digital rectal examination, and prior biopsy status provides a very high degree of discrimination for prostate cancer, compared with a PSA-based clinical algorithm, according to Dr. Daniel Lin.

The test (4Kscore test) was adapted from European studies which demonstrated that it is an accurate predictor of biopsy results, particularly for Gleason score 7 or greater disease, Dr. Lin of the University of Washington Medical Center, Seattle, reported during a late-breaking abstract session at the annual meeting of the American Urological Association.

In a prospective, blinded study, calibration of the 4Kscore algorithm in the first 300 patients enrolled from October 2013 to January 2014 was nearly perfect, compared with the European version, showing that the score works on an individual level, he said.

At one illustrative cut point, the score would have reduced the number of biopsies by 41%, with a negative-predictive value of 97%.

The test is of value at the population level, as well.

For high-grade disease, the 4Kscore test had a "very high and very robust" area under the curve of 0.82.

"The best comparator might be the [Prostate Cancer Prevention Trial] risk calculator, which takes into account age, PSA, Gleason grade, race, prior biopsy status, and the rectal examination," Dr. Lin said, explaining that findings with the two scores were "clearly nonoverlapping."

Even in the high-grade disease with a PSA of 2-10 in the "diagnostic gray zone," the 4Kscore test showed superiority for discrimination of high-grade disease.

A decision analysis demonstrated that clinical decision-making would be improved by the use of the 4Kscore test, he said.

Study subjects were 1,300 men scheduled for biopsy at any of 26 U.S. urology centers. Following phlebotomy, participants underwent at least a 10-core transrectal ultrasound-guided biopsy. The first 300 patients represented a calibration cohort, and the remaining 1,000 are part of a validation cohort.

The findings are of note, because controversy exists with respect to the use of PSA screening.

"We all know there are several challenges surrounding the early detection of prostate cancer, and particularly screening with PSA," Dr. Lin said, noting that positive screens lead to unnecessary biopsies.

In fact, about 60% of initial biopsies are negative, and about half of those that are positive are low-grade, potentially indolent disease, he said.

This, along with the fact that biopsies can be associated with complications and patient anxiety, has led to a negative perception of PSA screening among some medical organizations such as the U.S. Preventive Services Task Force, which has recommended against PSA screening of healthy men, despite evidence that PSA screening reduces mortality, Dr. Lin said.

Furthermore, treatment of low-risk disease is controversial, and data suggest that active surveillance is an acceptable strategy.

"Conversely, the treatment of intermediate- and high-risk disease has been supported by randomized, controlled trials, and there is a survival benefit for those men with intermediate- or high-risk disease," he said, noting that this underscores the importance of detecting high-grade disease.

The 4Kscore test addresses the controversies surrounding PSA screening and will address the concerns of policy makers who question prostate screening in general.

"The 4Kscore test yields superior performance to a clinical model based on the reduction of unnecessary biopsies and minimization of delay in diagnosing high-grade disease. The 4Kscore test is optimized for clinically relevant and actionable high-grade disease and can inform our decision making between the physician and patient, allowing for a unique personalization of risk. This will allow us to focus our efforts on treatment and evidence surrounding high-grade disease, which is clinically relevant," he concluded.

Funding for this study was provided by OPKO Diagnostics.

ORLANDO – A four kallikrein assay panel of human kallikrein and total, free, and intact prostate-specific antigen combined in an algorithm with age, digital rectal examination, and prior biopsy status provides a very high degree of discrimination for prostate cancer, compared with a PSA-based clinical algorithm, according to Dr. Daniel Lin.

The test (4Kscore test) was adapted from European studies which demonstrated that it is an accurate predictor of biopsy results, particularly for Gleason score 7 or greater disease, Dr. Lin of the University of Washington Medical Center, Seattle, reported during a late-breaking abstract session at the annual meeting of the American Urological Association.

In a prospective, blinded study, calibration of the 4Kscore algorithm in the first 300 patients enrolled from October 2013 to January 2014 was nearly perfect, compared with the European version, showing that the score works on an individual level, he said.

At one illustrative cut point, the score would have reduced the number of biopsies by 41%, with a negative-predictive value of 97%.

The test is of value at the population level, as well.

For high-grade disease, the 4Kscore test had a "very high and very robust" area under the curve of 0.82.

"The best comparator might be the [Prostate Cancer Prevention Trial] risk calculator, which takes into account age, PSA, Gleason grade, race, prior biopsy status, and the rectal examination," Dr. Lin said, explaining that findings with the two scores were "clearly nonoverlapping."

Even in the high-grade disease with a PSA of 2-10 in the "diagnostic gray zone," the 4Kscore test showed superiority for discrimination of high-grade disease.

A decision analysis demonstrated that clinical decision-making would be improved by the use of the 4Kscore test, he said.

Study subjects were 1,300 men scheduled for biopsy at any of 26 U.S. urology centers. Following phlebotomy, participants underwent at least a 10-core transrectal ultrasound-guided biopsy. The first 300 patients represented a calibration cohort, and the remaining 1,000 are part of a validation cohort.

The findings are of note, because controversy exists with respect to the use of PSA screening.

"We all know there are several challenges surrounding the early detection of prostate cancer, and particularly screening with PSA," Dr. Lin said, noting that positive screens lead to unnecessary biopsies.

In fact, about 60% of initial biopsies are negative, and about half of those that are positive are low-grade, potentially indolent disease, he said.

This, along with the fact that biopsies can be associated with complications and patient anxiety, has led to a negative perception of PSA screening among some medical organizations such as the U.S. Preventive Services Task Force, which has recommended against PSA screening of healthy men, despite evidence that PSA screening reduces mortality, Dr. Lin said.

Furthermore, treatment of low-risk disease is controversial, and data suggest that active surveillance is an acceptable strategy.

"Conversely, the treatment of intermediate- and high-risk disease has been supported by randomized, controlled trials, and there is a survival benefit for those men with intermediate- or high-risk disease," he said, noting that this underscores the importance of detecting high-grade disease.

The 4Kscore test addresses the controversies surrounding PSA screening and will address the concerns of policy makers who question prostate screening in general.

"The 4Kscore test yields superior performance to a clinical model based on the reduction of unnecessary biopsies and minimization of delay in diagnosing high-grade disease. The 4Kscore test is optimized for clinically relevant and actionable high-grade disease and can inform our decision making between the physician and patient, allowing for a unique personalization of risk. This will allow us to focus our efforts on treatment and evidence surrounding high-grade disease, which is clinically relevant," he concluded.

Funding for this study was provided by OPKO Diagnostics.

DESTIN, FLA. – Patients who present with what appears to be "puffy hand sign" should be carefully evaluated for systemic sclerosis, and if they also report Raynaud’s phenomenon and display acral or distal sclerosis and nailfold involvement, they should be treated aggressively, according to Dr. Ruth Ann Vleugels.

"We can really treat this disease if we catch it early and if we treat it aggressively," said Dr. Vleugels, director of the Autoimmune Skin Disease Program at Brigham & Women’s Hospital, Boston, and codirector of the Rheumatology-Dermatology Clinic at Boston Children’s Hospital.

The puffy hand sign will be apparent throughout the fingers and dorsal hand – not just in the joints – and patients may have limitation of movement when forming the prayer sign, she noted.

It is important to look for the other signs of disease as well, because puffy hands in the absence of Raynaud’s and nailfold involvement may represent eosinophilic fasciitis, which is sometimes misdiagnosed as systemic sclerosis, she explained at the annual Congress of Clinical Rheumatology.

When the signs and symptoms of systemic sclerosis are present, however, it is important to do a workup and begin treatment.

Typically, Dr. Vleugels said she starts with mycophenolate mofetil.

"This is one of those things that I have to encourage the rheumatologists I work with to consider," she said. "Often they don’t start treatment for cutaneous sclerosis because there’s no treatment that’s been proven to work. But I would argue that if we catch these patients early, we can really, really make a difference in their cutaneous sclerosis," she emphasized.

Based on the experience of researchers at Johns Hopkins University, Baltimore, Dr. Vleugels said she tries to get patients up to 3 g of mycophenolate mofetil if they can tolerate it, and then she tapers the dose to 2 g, and eventually discontinues treatment slowly over time if possible.

Counseling patients is particularly important for encouraging early treatment, because while some damage can’t be reversed, the process can be halted, Dr. Vleugels noted. She described one patient with total sclerosis of the fingers, which was worsening and starting to involve the dorsal hand and forearm, and was causing problems with wrist mobility.

"There is no miracle drug to bring this back – I can’t un-sclerose her fingers, but what we want to do first and foremost is halt the sclerosis process, and usually you can loosen the areas that are recently sclerosed," she said, noting that she uses mycophenolate mofetil not just for diffuse disease, but also for limited cutaneous sclerosis.

In a small, prospective observational study (J. Rheumatol. 2012;39:1241-7) mycophenolate mofetil was associated with a significant decrease in modified Rodnan Skin Score and body surface area of involvement in 25 patients with recent-onset, diffuse cutaneous systemic sclerosis, she said.

"They all also had stabilization of their PFTs [pulmonary function tests], which in this population is really actually excellent," she said.

Notably, onset of action was slow; patients continued to worsen for about 6 months before improvement was seen.

"So it’s very different than when we’re treating patients with other cutaneous diseases with mycophenolate, where we might give them a 3-month trial, and if that doesn’t work we go to something else," said Dr. Vleugels. "You really have to keep these patients on this drug, and it’s a 6- to 9-month window before you really start seeing your vast improvement," she said.

Additionally, there was biopsy evidence of mycophenolate mofetil activity in the study: The fibrosis associated with pain improved, the collagen appeared more normal, and there was a return of adnexal structures.

In addition to mycophenolate mofetil, systemic steroids can be used if a patient is experiencing rapid progression of disease. Steroids should be used with caution because of the potential increase in risk of renal crisis, but they may be warranted because of the delayed onset of action with mycophenolate mofetil, Dr. Vleugels said.

As for treating children, few data are available for guidance, so treatment is based on the findings in adults. As an example, Dr. Vleugels described her experience with an 8-year-old child with extensive sclerosis, who had a good response to mycophenolate mofetil.

In adults and children who can’t take mycophenolate mofetil, or who fail to respond, intravenous immunoglobulin is an option.

"If they can’t get mycophenolate, I have been using IVIG in some patients," Dr. Vleugels said, describing one patient who also had multiple sclerosis and who couldn’t be prescribed "anything else in terms of immunosuppression."

However, "I gave her IVIG, and she improved fairly well," she said.

One of the goals is to reduce longer-term complications.

"So we need to recognize the puffy hand sign and intervene based on skin disease alone – even if they don’t have active internal involvement, because that’s really the time when, hopefully, we can make a difference in these patients," she said.

Dr. Vleugels reported having no disclosures.

DESTIN, FLA. – Patients who present with what appears to be "puffy hand sign" should be carefully evaluated for systemic sclerosis, and if they also report Raynaud’s phenomenon and display acral or distal sclerosis and nailfold involvement, they should be treated aggressively, according to Dr. Ruth Ann Vleugels.

"We can really treat this disease if we catch it early and if we treat it aggressively," said Dr. Vleugels, director of the Autoimmune Skin Disease Program at Brigham & Women’s Hospital, Boston, and codirector of the Rheumatology-Dermatology Clinic at Boston Children’s Hospital.

The puffy hand sign will be apparent throughout the fingers and dorsal hand – not just in the joints – and patients may have limitation of movement when forming the prayer sign, she noted.

It is important to look for the other signs of disease as well, because puffy hands in the absence of Raynaud’s and nailfold involvement may represent eosinophilic fasciitis, which is sometimes misdiagnosed as systemic sclerosis, she explained at the annual Congress of Clinical Rheumatology.

When the signs and symptoms of systemic sclerosis are present, however, it is important to do a workup and begin treatment.

Typically, Dr. Vleugels said she starts with mycophenolate mofetil.

"This is one of those things that I have to encourage the rheumatologists I work with to consider," she said. "Often they don’t start treatment for cutaneous sclerosis because there’s no treatment that’s been proven to work. But I would argue that if we catch these patients early, we can really, really make a difference in their cutaneous sclerosis," she emphasized.

Based on the experience of researchers at Johns Hopkins University, Baltimore, Dr. Vleugels said she tries to get patients up to 3 g of mycophenolate mofetil if they can tolerate it, and then she tapers the dose to 2 g, and eventually discontinues treatment slowly over time if possible.

Counseling patients is particularly important for encouraging early treatment, because while some damage can’t be reversed, the process can be halted, Dr. Vleugels noted. She described one patient with total sclerosis of the fingers, which was worsening and starting to involve the dorsal hand and forearm, and was causing problems with wrist mobility.

"There is no miracle drug to bring this back – I can’t un-sclerose her fingers, but what we want to do first and foremost is halt the sclerosis process, and usually you can loosen the areas that are recently sclerosed," she said, noting that she uses mycophenolate mofetil not just for diffuse disease, but also for limited cutaneous sclerosis.

In a small, prospective observational study (J. Rheumatol. 2012;39:1241-7) mycophenolate mofetil was associated with a significant decrease in modified Rodnan Skin Score and body surface area of involvement in 25 patients with recent-onset, diffuse cutaneous systemic sclerosis, she said.

"They all also had stabilization of their PFTs [pulmonary function tests], which in this population is really actually excellent," she said.

Notably, onset of action was slow; patients continued to worsen for about 6 months before improvement was seen.

"So it’s very different than when we’re treating patients with other cutaneous diseases with mycophenolate, where we might give them a 3-month trial, and if that doesn’t work we go to something else," said Dr. Vleugels. "You really have to keep these patients on this drug, and it’s a 6- to 9-month window before you really start seeing your vast improvement," she said.

Additionally, there was biopsy evidence of mycophenolate mofetil activity in the study: The fibrosis associated with pain improved, the collagen appeared more normal, and there was a return of adnexal structures.

In addition to mycophenolate mofetil, systemic steroids can be used if a patient is experiencing rapid progression of disease. Steroids should be used with caution because of the potential increase in risk of renal crisis, but they may be warranted because of the delayed onset of action with mycophenolate mofetil, Dr. Vleugels said.

As for treating children, few data are available for guidance, so treatment is based on the findings in adults. As an example, Dr. Vleugels described her experience with an 8-year-old child with extensive sclerosis, who had a good response to mycophenolate mofetil.

In adults and children who can’t take mycophenolate mofetil, or who fail to respond, intravenous immunoglobulin is an option.

"If they can’t get mycophenolate, I have been using IVIG in some patients," Dr. Vleugels said, describing one patient who also had multiple sclerosis and who couldn’t be prescribed "anything else in terms of immunosuppression."

However, "I gave her IVIG, and she improved fairly well," she said.

One of the goals is to reduce longer-term complications.

"So we need to recognize the puffy hand sign and intervene based on skin disease alone – even if they don’t have active internal involvement, because that’s really the time when, hopefully, we can make a difference in these patients," she said.

Dr. Vleugels reported having no disclosures.

DESTIN, FLA. – Patients who present with what appears to be "puffy hand sign" should be carefully evaluated for systemic sclerosis, and if they also report Raynaud’s phenomenon and display acral or distal sclerosis and nailfold involvement, they should be treated aggressively, according to Dr. Ruth Ann Vleugels.

"We can really treat this disease if we catch it early and if we treat it aggressively," said Dr. Vleugels, director of the Autoimmune Skin Disease Program at Brigham & Women’s Hospital, Boston, and codirector of the Rheumatology-Dermatology Clinic at Boston Children’s Hospital.

The puffy hand sign will be apparent throughout the fingers and dorsal hand – not just in the joints – and patients may have limitation of movement when forming the prayer sign, she noted.

It is important to look for the other signs of disease as well, because puffy hands in the absence of Raynaud’s and nailfold involvement may represent eosinophilic fasciitis, which is sometimes misdiagnosed as systemic sclerosis, she explained at the annual Congress of Clinical Rheumatology.

When the signs and symptoms of systemic sclerosis are present, however, it is important to do a workup and begin treatment.

Typically, Dr. Vleugels said she starts with mycophenolate mofetil.

"This is one of those things that I have to encourage the rheumatologists I work with to consider," she said. "Often they don’t start treatment for cutaneous sclerosis because there’s no treatment that’s been proven to work. But I would argue that if we catch these patients early, we can really, really make a difference in their cutaneous sclerosis," she emphasized.

Based on the experience of researchers at Johns Hopkins University, Baltimore, Dr. Vleugels said she tries to get patients up to 3 g of mycophenolate mofetil if they can tolerate it, and then she tapers the dose to 2 g, and eventually discontinues treatment slowly over time if possible.

Counseling patients is particularly important for encouraging early treatment, because while some damage can’t be reversed, the process can be halted, Dr. Vleugels noted. She described one patient with total sclerosis of the fingers, which was worsening and starting to involve the dorsal hand and forearm, and was causing problems with wrist mobility.

"There is no miracle drug to bring this back – I can’t un-sclerose her fingers, but what we want to do first and foremost is halt the sclerosis process, and usually you can loosen the areas that are recently sclerosed," she said, noting that she uses mycophenolate mofetil not just for diffuse disease, but also for limited cutaneous sclerosis.

In a small, prospective observational study (J. Rheumatol. 2012;39:1241-7) mycophenolate mofetil was associated with a significant decrease in modified Rodnan Skin Score and body surface area of involvement in 25 patients with recent-onset, diffuse cutaneous systemic sclerosis, she said.

"They all also had stabilization of their PFTs [pulmonary function tests], which in this population is really actually excellent," she said.

Notably, onset of action was slow; patients continued to worsen for about 6 months before improvement was seen.

"So it’s very different than when we’re treating patients with other cutaneous diseases with mycophenolate, where we might give them a 3-month trial, and if that doesn’t work we go to something else," said Dr. Vleugels. "You really have to keep these patients on this drug, and it’s a 6- to 9-month window before you really start seeing your vast improvement," she said.

Additionally, there was biopsy evidence of mycophenolate mofetil activity in the study: The fibrosis associated with pain improved, the collagen appeared more normal, and there was a return of adnexal structures.

In addition to mycophenolate mofetil, systemic steroids can be used if a patient is experiencing rapid progression of disease. Steroids should be used with caution because of the potential increase in risk of renal crisis, but they may be warranted because of the delayed onset of action with mycophenolate mofetil, Dr. Vleugels said.

As for treating children, few data are available for guidance, so treatment is based on the findings in adults. As an example, Dr. Vleugels described her experience with an 8-year-old child with extensive sclerosis, who had a good response to mycophenolate mofetil.

In adults and children who can’t take mycophenolate mofetil, or who fail to respond, intravenous immunoglobulin is an option.

"If they can’t get mycophenolate, I have been using IVIG in some patients," Dr. Vleugels said, describing one patient who also had multiple sclerosis and who couldn’t be prescribed "anything else in terms of immunosuppression."

However, "I gave her IVIG, and she improved fairly well," she said.

One of the goals is to reduce longer-term complications.

"So we need to recognize the puffy hand sign and intervene based on skin disease alone – even if they don’t have active internal involvement, because that’s really the time when, hopefully, we can make a difference in these patients," she said.

Dr. Vleugels reported having no disclosures.

ORLANDO – Tumors detected following prostate-specific antigen screening in black men aged 40-54 years had more favorable clinico-pathologic characteristics than those detected in black men aged 55-70 years, according to a study of more than 2,700 veterans.

The findings provide clinical support for the recommendation that black men who desire prostate cancer screening undergo prostate-specific antigen (PSA) testing at an earlier age than is suggested for white men – a recommendation based primarily on observed racial disparities in prostate cancer outcomes for men older than 50 years of age, Amanda Saltzman, Pharm.D., reported at the annual meeting of the American Urological Association.

Among the observed racial disparities in outcomes are higher tumor grade, greater likelihood of nonlocalized disease, and advanced-stage prostate cancer at diagnosis, as well as higher tumor volume in prostatectomy specimens, higher index PSA levels, younger age at diagnosis, lower likelihood of low-risk prognostic data, and higher mortality. However, it has been unclear whether earlier testing confers a survival benefit, she said.

In the current study, Dr. Saltzman and her colleagues sought to determine whether the diagnosis of tumors with characteristics associated with increased mortality was less likely in black men tested at ages 40-54 years, compared with those tested at ages 55-70 years, and compared with white men tested at ages 40-54 years in an "equal insurance coverage system," Dr. Saltzman of Louisiana State University, New Orleans explained during a press briefing at the meeting.

The men were part of a cohort of more than 231,000 otherwise healthy veterans aged 40-70 years who underwent PSA testing between October 2000 and September 2007. A total of 1,044 black veterans and 1,700 white veterans were diagnosed with prostate cancer. A total of 397 black men aged 40-54 years were compared with 647 black men aged 55-70 years and with the white veterans aged 40-54 years.

No difference was seen between the younger and older black cohort with respect to prebiopsy PSA. For example, 9.3% and 9.4% of men in the groups, respectively, had PSA greater than 20 ng/mL.

"When we looked at our young black cohort and our white cohort, however, there was a statistically significant difference, with our blacks having a higher index PSA [9.3% younger blacks vs. 6% whites had PSA greater than 20 ng/mL]. When we looked at biopsy Gleason sums, there was a significant difference between our older blacks and our younger blacks, with our older blacks tending to have higher Gleason scores than the younger blacks [15% vs. 12% had scores greater than eight, for example]," Dr. Saltzman said.

There was no difference between the young black veterans and the white veterans in Gleason scores, and no difference between any of the groups with respect to tumor stage.

In the older blacks, there was a nonsignificant trend toward higher risk, compared with younger blacks.

"This trend persisted ... with our younger black men tending to be at higher risk than our white veterans," she noted.

"PSA testing of black men younger than age 55 provides a benefit specifically with respect to Gleason score at diagnosis. We know that Gleason sum strongly predicts disease-free survival in men with clinical localized disease. In contrast to prior general population studies, we did not observe any racial disparities with respect to clinical stage, tumor grade, or D’Amicorisk stratification for prostate cancer in veterans aged 40-54, so our equal insurance coverage seems to have eliminated some of the previously reported disparities," she said, adding that she and her colleagues hope to further explore whether earlier testing reduces prostate cancer deaths in blacks, and whether equal insurance coverage and equal access to screening and detection tools eliminates previously reported racial disparities in prostate cancer death.

The current findings provide the first evidence to support the current recommendations for screening at an earlier age in black men, she concluded, adding: "I would definitely advocate for screening black men early. The specific age is unclear, but certainly before age 55."

Dr. Saltzman reported having no disclosures.

ORLANDO – Tumors detected following prostate-specific antigen screening in black men aged 40-54 years had more favorable clinico-pathologic characteristics than those detected in black men aged 55-70 years, according to a study of more than 2,700 veterans.

The findings provide clinical support for the recommendation that black men who desire prostate cancer screening undergo prostate-specific antigen (PSA) testing at an earlier age than is suggested for white men – a recommendation based primarily on observed racial disparities in prostate cancer outcomes for men older than 50 years of age, Amanda Saltzman, Pharm.D., reported at the annual meeting of the American Urological Association.

Among the observed racial disparities in outcomes are higher tumor grade, greater likelihood of nonlocalized disease, and advanced-stage prostate cancer at diagnosis, as well as higher tumor volume in prostatectomy specimens, higher index PSA levels, younger age at diagnosis, lower likelihood of low-risk prognostic data, and higher mortality. However, it has been unclear whether earlier testing confers a survival benefit, she said.

In the current study, Dr. Saltzman and her colleagues sought to determine whether the diagnosis of tumors with characteristics associated with increased mortality was less likely in black men tested at ages 40-54 years, compared with those tested at ages 55-70 years, and compared with white men tested at ages 40-54 years in an "equal insurance coverage system," Dr. Saltzman of Louisiana State University, New Orleans explained during a press briefing at the meeting.

The men were part of a cohort of more than 231,000 otherwise healthy veterans aged 40-70 years who underwent PSA testing between October 2000 and September 2007. A total of 1,044 black veterans and 1,700 white veterans were diagnosed with prostate cancer. A total of 397 black men aged 40-54 years were compared with 647 black men aged 55-70 years and with the white veterans aged 40-54 years.

No difference was seen between the younger and older black cohort with respect to prebiopsy PSA. For example, 9.3% and 9.4% of men in the groups, respectively, had PSA greater than 20 ng/mL.

"When we looked at our young black cohort and our white cohort, however, there was a statistically significant difference, with our blacks having a higher index PSA [9.3% younger blacks vs. 6% whites had PSA greater than 20 ng/mL]. When we looked at biopsy Gleason sums, there was a significant difference between our older blacks and our younger blacks, with our older blacks tending to have higher Gleason scores than the younger blacks [15% vs. 12% had scores greater than eight, for example]," Dr. Saltzman said.

There was no difference between the young black veterans and the white veterans in Gleason scores, and no difference between any of the groups with respect to tumor stage.

In the older blacks, there was a nonsignificant trend toward higher risk, compared with younger blacks.

"This trend persisted ... with our younger black men tending to be at higher risk than our white veterans," she noted.

"PSA testing of black men younger than age 55 provides a benefit specifically with respect to Gleason score at diagnosis. We know that Gleason sum strongly predicts disease-free survival in men with clinical localized disease. In contrast to prior general population studies, we did not observe any racial disparities with respect to clinical stage, tumor grade, or D’Amicorisk stratification for prostate cancer in veterans aged 40-54, so our equal insurance coverage seems to have eliminated some of the previously reported disparities," she said, adding that she and her colleagues hope to further explore whether earlier testing reduces prostate cancer deaths in blacks, and whether equal insurance coverage and equal access to screening and detection tools eliminates previously reported racial disparities in prostate cancer death.

The current findings provide the first evidence to support the current recommendations for screening at an earlier age in black men, she concluded, adding: "I would definitely advocate for screening black men early. The specific age is unclear, but certainly before age 55."

Dr. Saltzman reported having no disclosures.

ORLANDO – Tumors detected following prostate-specific antigen screening in black men aged 40-54 years had more favorable clinico-pathologic characteristics than those detected in black men aged 55-70 years, according to a study of more than 2,700 veterans.

The findings provide clinical support for the recommendation that black men who desire prostate cancer screening undergo prostate-specific antigen (PSA) testing at an earlier age than is suggested for white men – a recommendation based primarily on observed racial disparities in prostate cancer outcomes for men older than 50 years of age, Amanda Saltzman, Pharm.D., reported at the annual meeting of the American Urological Association.

Among the observed racial disparities in outcomes are higher tumor grade, greater likelihood of nonlocalized disease, and advanced-stage prostate cancer at diagnosis, as well as higher tumor volume in prostatectomy specimens, higher index PSA levels, younger age at diagnosis, lower likelihood of low-risk prognostic data, and higher mortality. However, it has been unclear whether earlier testing confers a survival benefit, she said.

In the current study, Dr. Saltzman and her colleagues sought to determine whether the diagnosis of tumors with characteristics associated with increased mortality was less likely in black men tested at ages 40-54 years, compared with those tested at ages 55-70 years, and compared with white men tested at ages 40-54 years in an "equal insurance coverage system," Dr. Saltzman of Louisiana State University, New Orleans explained during a press briefing at the meeting.

The men were part of a cohort of more than 231,000 otherwise healthy veterans aged 40-70 years who underwent PSA testing between October 2000 and September 2007. A total of 1,044 black veterans and 1,700 white veterans were diagnosed with prostate cancer. A total of 397 black men aged 40-54 years were compared with 647 black men aged 55-70 years and with the white veterans aged 40-54 years.

No difference was seen between the younger and older black cohort with respect to prebiopsy PSA. For example, 9.3% and 9.4% of men in the groups, respectively, had PSA greater than 20 ng/mL.

"When we looked at our young black cohort and our white cohort, however, there was a statistically significant difference, with our blacks having a higher index PSA [9.3% younger blacks vs. 6% whites had PSA greater than 20 ng/mL]. When we looked at biopsy Gleason sums, there was a significant difference between our older blacks and our younger blacks, with our older blacks tending to have higher Gleason scores than the younger blacks [15% vs. 12% had scores greater than eight, for example]," Dr. Saltzman said.

There was no difference between the young black veterans and the white veterans in Gleason scores, and no difference between any of the groups with respect to tumor stage.

In the older blacks, there was a nonsignificant trend toward higher risk, compared with younger blacks.

"This trend persisted ... with our younger black men tending to be at higher risk than our white veterans," she noted.

"PSA testing of black men younger than age 55 provides a benefit specifically with respect to Gleason score at diagnosis. We know that Gleason sum strongly predicts disease-free survival in men with clinical localized disease. In contrast to prior general population studies, we did not observe any racial disparities with respect to clinical stage, tumor grade, or D’Amicorisk stratification for prostate cancer in veterans aged 40-54, so our equal insurance coverage seems to have eliminated some of the previously reported disparities," she said, adding that she and her colleagues hope to further explore whether earlier testing reduces prostate cancer deaths in blacks, and whether equal insurance coverage and equal access to screening and detection tools eliminates previously reported racial disparities in prostate cancer death.

The current findings provide the first evidence to support the current recommendations for screening at an earlier age in black men, she concluded, adding: "I would definitely advocate for screening black men early. The specific age is unclear, but certainly before age 55."

Dr. Saltzman reported having no disclosures.

CHICAGO – A novel composite prognostic index score helped predict the onset of labor in a retrospective cohort of patients with preterm premature rupture of membranes.

In a separate study, researchers identified three independent predictors of emergent outcomes in patients with preterm premature rupture of membranes (PPROM).

The findings of both studies were presented in posters at the annual meeting of the American Congress of Obstetricians and Gynecologists.

The composite prognostic index score in the first study predicted the likelihood of labor within 12 hours while maintaining a significantly high negative predictive value in 78 patients between 24 and 34 weeks of gestation who were admitted with PPROM over a 2-year period, according to Dr. Yelena Feldman of Trihealth, Cincinnati.

In fact, differences in all variables included in the score were significant at 12 hours prior to labor, she noted.

Variables included as part of the score were deepest vertical pocket of amniotic fluid by ultrasound, fetal heart rate, changes in fetal heart rate variability, presence of decelerations, number of contractions, vaginal bleeding, and record of nursing concern. Each variable was scored at four time points prior to spontaneous labor onset (48, 36, 24, and 12 hours), and a model using the presence of dichotomous variables at 12 hours prior to labor onset was used to make the composite score.

A binary model with the outcome of 12 hours until labor onset had the best results (91.9% specificity; 51.25% sensitivity, 85% negative predictive value, and 67.8% positive predictive value).

Each variable was assigned a number of points based on its beta coefficient in the multivariate model, and the patient could be assigned a score based on the presence of these characteristics.

"The value would correspond to the risk of labor starting within 12 hours," she noted.

The cutoff score, determined by the receiver operating characteristic curves that signified the likelihood of starting labor in 12 hours, was 18, Dr. Feldman explained in the poster.

A score of 18 yielded a negative predictive value of 90.5%, a positive predictive value of 52%, and a sensitivity of 80.9%.

"This composite score may serve as a useful tool in clinical settings where patients admitted with PPROM need decisions regarding patient transfer, administering magnesium sulfate for neuroprotection, or administering a rescue dose of steroid," she concluded.

In the second study, Dr. Tripp Nelson of the Medical University of South Carolina, Charleston, found that malpresentation, bleeding, and sexually transmitted infection each predicted emergent outcomes in PPROM patients.

An admission test utilizing these three factors had 96.4% negative predictive value for emergent outcomes, 57.4% positive predictive value, 91% specificity, and 75.9% sensitivity. For the retrospective case-control study, Dr. Nelson and his colleagues identified 624 subjects, including 83 with at least one emergent outcome.

The emergent group had significantly higher rates of perinatal death and acidosis, and while bivariable comparison showed increased incidence of leukocytosis, urinary tract infection, sexually transmitted infection (STI), malpresentation, latency, vaginal bleeding, and fundal tenderness; only vaginal bleeding, STI, and malpresentation remained significant on logistic regression analysis.

Further randomized testing is needed for model validation, Dr. Nelson concluded.

The authors of both studies reported having no disclosures.

CHICAGO – A novel composite prognostic index score helped predict the onset of labor in a retrospective cohort of patients with preterm premature rupture of membranes.

In a separate study, researchers identified three independent predictors of emergent outcomes in patients with preterm premature rupture of membranes (PPROM).

The findings of both studies were presented in posters at the annual meeting of the American Congress of Obstetricians and Gynecologists.

The composite prognostic index score in the first study predicted the likelihood of labor within 12 hours while maintaining a significantly high negative predictive value in 78 patients between 24 and 34 weeks of gestation who were admitted with PPROM over a 2-year period, according to Dr. Yelena Feldman of Trihealth, Cincinnati.

In fact, differences in all variables included in the score were significant at 12 hours prior to labor, she noted.

Variables included as part of the score were deepest vertical pocket of amniotic fluid by ultrasound, fetal heart rate, changes in fetal heart rate variability, presence of decelerations, number of contractions, vaginal bleeding, and record of nursing concern. Each variable was scored at four time points prior to spontaneous labor onset (48, 36, 24, and 12 hours), and a model using the presence of dichotomous variables at 12 hours prior to labor onset was used to make the composite score.

A binary model with the outcome of 12 hours until labor onset had the best results (91.9% specificity; 51.25% sensitivity, 85% negative predictive value, and 67.8% positive predictive value).

Each variable was assigned a number of points based on its beta coefficient in the multivariate model, and the patient could be assigned a score based on the presence of these characteristics.

"The value would correspond to the risk of labor starting within 12 hours," she noted.

The cutoff score, determined by the receiver operating characteristic curves that signified the likelihood of starting labor in 12 hours, was 18, Dr. Feldman explained in the poster.

A score of 18 yielded a negative predictive value of 90.5%, a positive predictive value of 52%, and a sensitivity of 80.9%.

"This composite score may serve as a useful tool in clinical settings where patients admitted with PPROM need decisions regarding patient transfer, administering magnesium sulfate for neuroprotection, or administering a rescue dose of steroid," she concluded.

In the second study, Dr. Tripp Nelson of the Medical University of South Carolina, Charleston, found that malpresentation, bleeding, and sexually transmitted infection each predicted emergent outcomes in PPROM patients.

An admission test utilizing these three factors had 96.4% negative predictive value for emergent outcomes, 57.4% positive predictive value, 91% specificity, and 75.9% sensitivity. For the retrospective case-control study, Dr. Nelson and his colleagues identified 624 subjects, including 83 with at least one emergent outcome.

The emergent group had significantly higher rates of perinatal death and acidosis, and while bivariable comparison showed increased incidence of leukocytosis, urinary tract infection, sexually transmitted infection (STI), malpresentation, latency, vaginal bleeding, and fundal tenderness; only vaginal bleeding, STI, and malpresentation remained significant on logistic regression analysis.

Further randomized testing is needed for model validation, Dr. Nelson concluded.

The authors of both studies reported having no disclosures.

CHICAGO – A novel composite prognostic index score helped predict the onset of labor in a retrospective cohort of patients with preterm premature rupture of membranes.

In a separate study, researchers identified three independent predictors of emergent outcomes in patients with preterm premature rupture of membranes (PPROM).

The findings of both studies were presented in posters at the annual meeting of the American Congress of Obstetricians and Gynecologists.

The composite prognostic index score in the first study predicted the likelihood of labor within 12 hours while maintaining a significantly high negative predictive value in 78 patients between 24 and 34 weeks of gestation who were admitted with PPROM over a 2-year period, according to Dr. Yelena Feldman of Trihealth, Cincinnati.

In fact, differences in all variables included in the score were significant at 12 hours prior to labor, she noted.

Variables included as part of the score were deepest vertical pocket of amniotic fluid by ultrasound, fetal heart rate, changes in fetal heart rate variability, presence of decelerations, number of contractions, vaginal bleeding, and record of nursing concern. Each variable was scored at four time points prior to spontaneous labor onset (48, 36, 24, and 12 hours), and a model using the presence of dichotomous variables at 12 hours prior to labor onset was used to make the composite score.

A binary model with the outcome of 12 hours until labor onset had the best results (91.9% specificity; 51.25% sensitivity, 85% negative predictive value, and 67.8% positive predictive value).

Each variable was assigned a number of points based on its beta coefficient in the multivariate model, and the patient could be assigned a score based on the presence of these characteristics.

"The value would correspond to the risk of labor starting within 12 hours," she noted.

The cutoff score, determined by the receiver operating characteristic curves that signified the likelihood of starting labor in 12 hours, was 18, Dr. Feldman explained in the poster.

A score of 18 yielded a negative predictive value of 90.5%, a positive predictive value of 52%, and a sensitivity of 80.9%.

"This composite score may serve as a useful tool in clinical settings where patients admitted with PPROM need decisions regarding patient transfer, administering magnesium sulfate for neuroprotection, or administering a rescue dose of steroid," she concluded.

In the second study, Dr. Tripp Nelson of the Medical University of South Carolina, Charleston, found that malpresentation, bleeding, and sexually transmitted infection each predicted emergent outcomes in PPROM patients.

An admission test utilizing these three factors had 96.4% negative predictive value for emergent outcomes, 57.4% positive predictive value, 91% specificity, and 75.9% sensitivity. For the retrospective case-control study, Dr. Nelson and his colleagues identified 624 subjects, including 83 with at least one emergent outcome.

The emergent group had significantly higher rates of perinatal death and acidosis, and while bivariable comparison showed increased incidence of leukocytosis, urinary tract infection, sexually transmitted infection (STI), malpresentation, latency, vaginal bleeding, and fundal tenderness; only vaginal bleeding, STI, and malpresentation remained significant on logistic regression analysis.

Further randomized testing is needed for model validation, Dr. Nelson concluded.

The authors of both studies reported having no disclosures.

ORLANDO – A single prostate specific antigen level measurement before age 60 years in the setting of opportunistic screening predicted lethal prostate cancer in later life, according to findings from a nested case-control study involving Physicians’ Health Study participants.

The findings, which confirm prior observations that midlife PSA levels predict subsequent development of lethal prostate cancer in an unscreened population – and which extend the findings to a cohort where opportunistic screening occurs, could have implications for reducing unnecessary screening, biopsy, and treatment, Dr. Mark A. Preston reported at the annual meeting of the American Urological Association.

Of 14,916 men from the randomized, controlled Physicians’ Health Study who submitted a blood specimen prior to enrollment, 234 with total PSA levels available prior to age 60 years had prostate cancer diagnosed between 1983 and 1993, and 711 served as age-matched controls.

As of follow-up through 2012, metastatic or fatal disease had developed in 60 case patients.

"We went on to ask three main clinical questions about how [midlife PSA] might be clinically relevant," Dr. Preston, who is a urologist at Massachusetts General Hospital, Boston, said during a press briefing at the meeting.

The first question was whether baseline PSA predicts lethal cancer.

The median PSA levels at three age groups evaluated in the study (40-50 years, 50-55 years, and 55-60 years) were 0.68 ng/mL, 0.88 ng/mL, and 0.96 ng/mL, respectively, he said.

Using men with a PSA below the median as a reference group, the risk of lethal prostate cancer for those with PSA above the 75th percentile was "quite significant," with those aged 40-50 years having a sixfold increased risk, those aged 50-55 years having a fourfold increased risk, and those aged 55-60 having a 10-fold increased risk, he noted.

"This was even more significant for those with PSA above the 90th percentile," he said.

The next question was whether those with a very low PSA before age 60 years could forego further PSA testing.

Compared with men with a PSA above the median, those with PSA below the 25th percentile had a very low risk of lethal prostate cancer (odds ratio, 1.6), he said.

The third question was whether men with one very low PSA level measurement between ages 40-50 years could forego any further PSA testing.

"The numbers were small, but what we did find was that there were still men who had a PSA level at that very low level who still went on to die from prostate cancer at some point," he said, noting that this likely means that one PSA measurement is inadequate.

That one PSA, however, may be useful for risk stratification, allowing for a longer interval between testing for those with such low risk.

Early PSA was found in this study to have very good predictive value for lethal prostate cancer, with an area under the curve of about 0.80 for all of the age groups, he said.

"We concluded that a single baseline PSA among men at midlife strongly predicts the subsequent development of lethal prostate cancer in a U.S. population subject to opportunistic PSA screening, and also that there was no lower limit of PSA baseline at which no men developed lethal prostate cancer," he said.

The findings are notable, given the current controversy over the usefulness of PSA screening.

"The reason these data are so important – and this dovetails with a lot of other data that are out there – is that we’re trying to make a more sensible screening strategy for men," according to Dr. Scott E. Eggener, director of translational and outcomes research, section of urology at the University of Chicago, who moderated the press briefing.

This is very similar to how colonoscopy is used, he said, explaining that patients get a baseline colonoscopy and the findings determine the interval needed for follow-up.

"We’ve never done that in PSA screening for prostate cancer. It has always started at a certain age, everyone is treated the same way, it’s done once a year (at least in the United States)," he said.

The current data, when considered in light of other similar studies, are very compelling in that they demonstrate the need for a more individualized, tailored approach to screening based on factors such as race, family history, age, and baseline PSA.

"These data suggest that baseline PSA is an incredibly powerful predictor of events that are maybe destined to happen 10 or 20 years down the road, and we need to incorporate that in our thinking about screening," Dr. Eggener said.

Dr. Preston reported having no disclosures. Dr. Eggener has been a consultant, adviser, lecturer, investigator, and/or proctor for Genomic Health, Intuitive Surgical Janssen Pharmaceuticals, and Myriad Genetics.

ORLANDO – A single prostate specific antigen level measurement before age 60 years in the setting of opportunistic screening predicted lethal prostate cancer in later life, according to findings from a nested case-control study involving Physicians’ Health Study participants.

The findings, which confirm prior observations that midlife PSA levels predict subsequent development of lethal prostate cancer in an unscreened population – and which extend the findings to a cohort where opportunistic screening occurs, could have implications for reducing unnecessary screening, biopsy, and treatment, Dr. Mark A. Preston reported at the annual meeting of the American Urological Association.

Of 14,916 men from the randomized, controlled Physicians’ Health Study who submitted a blood specimen prior to enrollment, 234 with total PSA levels available prior to age 60 years had prostate cancer diagnosed between 1983 and 1993, and 711 served as age-matched controls.

As of follow-up through 2012, metastatic or fatal disease had developed in 60 case patients.

"We went on to ask three main clinical questions about how [midlife PSA] might be clinically relevant," Dr. Preston, who is a urologist at Massachusetts General Hospital, Boston, said during a press briefing at the meeting.

The first question was whether baseline PSA predicts lethal cancer.

The median PSA levels at three age groups evaluated in the study (40-50 years, 50-55 years, and 55-60 years) were 0.68 ng/mL, 0.88 ng/mL, and 0.96 ng/mL, respectively, he said.

Using men with a PSA below the median as a reference group, the risk of lethal prostate cancer for those with PSA above the 75th percentile was "quite significant," with those aged 40-50 years having a sixfold increased risk, those aged 50-55 years having a fourfold increased risk, and those aged 55-60 having a 10-fold increased risk, he noted.

"This was even more significant for those with PSA above the 90th percentile," he said.

The next question was whether those with a very low PSA before age 60 years could forego further PSA testing.

Compared with men with a PSA above the median, those with PSA below the 25th percentile had a very low risk of lethal prostate cancer (odds ratio, 1.6), he said.

The third question was whether men with one very low PSA level measurement between ages 40-50 years could forego any further PSA testing.

"The numbers were small, but what we did find was that there were still men who had a PSA level at that very low level who still went on to die from prostate cancer at some point," he said, noting that this likely means that one PSA measurement is inadequate.

That one PSA, however, may be useful for risk stratification, allowing for a longer interval between testing for those with such low risk.

Early PSA was found in this study to have very good predictive value for lethal prostate cancer, with an area under the curve of about 0.80 for all of the age groups, he said.

"We concluded that a single baseline PSA among men at midlife strongly predicts the subsequent development of lethal prostate cancer in a U.S. population subject to opportunistic PSA screening, and also that there was no lower limit of PSA baseline at which no men developed lethal prostate cancer," he said.

The findings are notable, given the current controversy over the usefulness of PSA screening.

"The reason these data are so important – and this dovetails with a lot of other data that are out there – is that we’re trying to make a more sensible screening strategy for men," according to Dr. Scott E. Eggener, director of translational and outcomes research, section of urology at the University of Chicago, who moderated the press briefing.

This is very similar to how colonoscopy is used, he said, explaining that patients get a baseline colonoscopy and the findings determine the interval needed for follow-up.

"We’ve never done that in PSA screening for prostate cancer. It has always started at a certain age, everyone is treated the same way, it’s done once a year (at least in the United States)," he said.

The current data, when considered in light of other similar studies, are very compelling in that they demonstrate the need for a more individualized, tailored approach to screening based on factors such as race, family history, age, and baseline PSA.

"These data suggest that baseline PSA is an incredibly powerful predictor of events that are maybe destined to happen 10 or 20 years down the road, and we need to incorporate that in our thinking about screening," Dr. Eggener said.

Dr. Preston reported having no disclosures. Dr. Eggener has been a consultant, adviser, lecturer, investigator, and/or proctor for Genomic Health, Intuitive Surgical Janssen Pharmaceuticals, and Myriad Genetics.

ORLANDO – A single prostate specific antigen level measurement before age 60 years in the setting of opportunistic screening predicted lethal prostate cancer in later life, according to findings from a nested case-control study involving Physicians’ Health Study participants.

The findings, which confirm prior observations that midlife PSA levels predict subsequent development of lethal prostate cancer in an unscreened population – and which extend the findings to a cohort where opportunistic screening occurs, could have implications for reducing unnecessary screening, biopsy, and treatment, Dr. Mark A. Preston reported at the annual meeting of the American Urological Association.

Of 14,916 men from the randomized, controlled Physicians’ Health Study who submitted a blood specimen prior to enrollment, 234 with total PSA levels available prior to age 60 years had prostate cancer diagnosed between 1983 and 1993, and 711 served as age-matched controls.

As of follow-up through 2012, metastatic or fatal disease had developed in 60 case patients.

"We went on to ask three main clinical questions about how [midlife PSA] might be clinically relevant," Dr. Preston, who is a urologist at Massachusetts General Hospital, Boston, said during a press briefing at the meeting.

The first question was whether baseline PSA predicts lethal cancer.

The median PSA levels at three age groups evaluated in the study (40-50 years, 50-55 years, and 55-60 years) were 0.68 ng/mL, 0.88 ng/mL, and 0.96 ng/mL, respectively, he said.

Using men with a PSA below the median as a reference group, the risk of lethal prostate cancer for those with PSA above the 75th percentile was "quite significant," with those aged 40-50 years having a sixfold increased risk, those aged 50-55 years having a fourfold increased risk, and those aged 55-60 having a 10-fold increased risk, he noted.

"This was even more significant for those with PSA above the 90th percentile," he said.

The next question was whether those with a very low PSA before age 60 years could forego further PSA testing.

Compared with men with a PSA above the median, those with PSA below the 25th percentile had a very low risk of lethal prostate cancer (odds ratio, 1.6), he said.

The third question was whether men with one very low PSA level measurement between ages 40-50 years could forego any further PSA testing.

"The numbers were small, but what we did find was that there were still men who had a PSA level at that very low level who still went on to die from prostate cancer at some point," he said, noting that this likely means that one PSA measurement is inadequate.

That one PSA, however, may be useful for risk stratification, allowing for a longer interval between testing for those with such low risk.

Early PSA was found in this study to have very good predictive value for lethal prostate cancer, with an area under the curve of about 0.80 for all of the age groups, he said.

"We concluded that a single baseline PSA among men at midlife strongly predicts the subsequent development of lethal prostate cancer in a U.S. population subject to opportunistic PSA screening, and also that there was no lower limit of PSA baseline at which no men developed lethal prostate cancer," he said.

The findings are notable, given the current controversy over the usefulness of PSA screening.

"The reason these data are so important – and this dovetails with a lot of other data that are out there – is that we’re trying to make a more sensible screening strategy for men," according to Dr. Scott E. Eggener, director of translational and outcomes research, section of urology at the University of Chicago, who moderated the press briefing.

This is very similar to how colonoscopy is used, he said, explaining that patients get a baseline colonoscopy and the findings determine the interval needed for follow-up.

"We’ve never done that in PSA screening for prostate cancer. It has always started at a certain age, everyone is treated the same way, it’s done once a year (at least in the United States)," he said.

The current data, when considered in light of other similar studies, are very compelling in that they demonstrate the need for a more individualized, tailored approach to screening based on factors such as race, family history, age, and baseline PSA.

"These data suggest that baseline PSA is an incredibly powerful predictor of events that are maybe destined to happen 10 or 20 years down the road, and we need to incorporate that in our thinking about screening," Dr. Eggener said.

Dr. Preston reported having no disclosures. Dr. Eggener has been a consultant, adviser, lecturer, investigator, and/or proctor for Genomic Health, Intuitive Surgical Janssen Pharmaceuticals, and Myriad Genetics.