AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

The results of a hepatitis C virus screening program in a suburban New Jersey acute opioid detoxification program reveal that, despite the ease of access to HCV screening and the availability of curative therapies, linkage to care after detection of infection in persons who inject drugs continues to present a challenge.

Eda Akyar, a clinical research coordinator at ID Care, New Jersey’s largest network of infectious disease specialists, and her colleagues examined the results of an HIV, HCV, and HBV infection screening program instituted between Oct. 1, 2014, and June 9, 2015, for patients admitted to an acute opioid detoxification program at Princeton House in suburban New Jersey. Study goals included assessing the prevalence of HIV, HCV, and HBV infections for these patients, the HCV genotype (GT) carried, and the subsequent linkage to care after discharge from the program. The report was published online April 13 in Emerging Infectious Diseases.

Jezperklauzen/ThinkStock

During the screening period, patients representing 10 of New Jersey’s 21 counties were tested for the presence of HCV antibodies. Approximately two-thirds of all study participants (66.6%) were between 17 and 35 years of age. In this important age demographic, 237 patients (41.4%) screened positive for HCV antibodies, and 187 were available for further study.

HCV viral load data were available from 172 patients (92.0%), with approximately one-fifth (18.6%) screening undetectable. The HCV GTs obtained from 102 patients revealed that most (62.7%) were GT1a, followed by GT3 (25.5%). In a very surprising result, all HCV antibody positive patients were also HIV antibody negative, the researchers noted.

Regarding linkage to care, 16 of the patients (8.6%) in the 17- to 35-year-old age group attended outpatient follow-up appointments, with three (1.6%) starting on an oral, direct-acting antiviral treatment regimen. Two of these three patients were nonadherent to their treatment regimens. Two additional patients expressed willingness to accept treatment, but were denied their prescriptions by their insurance providers. None of the other participants returned for continued care.

The authors said that their results indicated a high prevalence of HCV among young suburban heroin users attending an acute detoxification program serving a wide geographic area, suggesting that New Jersey is part of the second wave of HCV infection following that seen in those born from 1946 to 1964. They also highlighted their findings of a GT3 prevalence more than twice the national average, a complete lack of HIV infection in a population known to be susceptible to it, and disappointing linkage to care outcomes.

The authors said that easy-to-use curative therapy should underscore a need for improved linkage to care and treatment of HCV-infected persons who inject drugs as part of an important public health effort to prevent its continued spread.

This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Conflict of interest information was not disclosed.

The results of a hepatitis C virus screening program in a suburban New Jersey acute opioid detoxification program reveal that, despite the ease of access to HCV screening and the availability of curative therapies, linkage to care after detection of infection in persons who inject drugs continues to present a challenge.

Eda Akyar, a clinical research coordinator at ID Care, New Jersey’s largest network of infectious disease specialists, and her colleagues examined the results of an HIV, HCV, and HBV infection screening program instituted between Oct. 1, 2014, and June 9, 2015, for patients admitted to an acute opioid detoxification program at Princeton House in suburban New Jersey. Study goals included assessing the prevalence of HIV, HCV, and HBV infections for these patients, the HCV genotype (GT) carried, and the subsequent linkage to care after discharge from the program. The report was published online April 13 in Emerging Infectious Diseases.

Jezperklauzen/ThinkStock

During the screening period, patients representing 10 of New Jersey’s 21 counties were tested for the presence of HCV antibodies. Approximately two-thirds of all study participants (66.6%) were between 17 and 35 years of age. In this important age demographic, 237 patients (41.4%) screened positive for HCV antibodies, and 187 were available for further study.

HCV viral load data were available from 172 patients (92.0%), with approximately one-fifth (18.6%) screening undetectable. The HCV GTs obtained from 102 patients revealed that most (62.7%) were GT1a, followed by GT3 (25.5%). In a very surprising result, all HCV antibody positive patients were also HIV antibody negative, the researchers noted.

Regarding linkage to care, 16 of the patients (8.6%) in the 17- to 35-year-old age group attended outpatient follow-up appointments, with three (1.6%) starting on an oral, direct-acting antiviral treatment regimen. Two of these three patients were nonadherent to their treatment regimens. Two additional patients expressed willingness to accept treatment, but were denied their prescriptions by their insurance providers. None of the other participants returned for continued care.

The authors said that their results indicated a high prevalence of HCV among young suburban heroin users attending an acute detoxification program serving a wide geographic area, suggesting that New Jersey is part of the second wave of HCV infection following that seen in those born from 1946 to 1964. They also highlighted their findings of a GT3 prevalence more than twice the national average, a complete lack of HIV infection in a population known to be susceptible to it, and disappointing linkage to care outcomes.

The authors said that easy-to-use curative therapy should underscore a need for improved linkage to care and treatment of HCV-infected persons who inject drugs as part of an important public health effort to prevent its continued spread.

This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Conflict of interest information was not disclosed.

The results of a hepatitis C virus screening program in a suburban New Jersey acute opioid detoxification program reveal that, despite the ease of access to HCV screening and the availability of curative therapies, linkage to care after detection of infection in persons who inject drugs continues to present a challenge.

Eda Akyar, a clinical research coordinator at ID Care, New Jersey’s largest network of infectious disease specialists, and her colleagues examined the results of an HIV, HCV, and HBV infection screening program instituted between Oct. 1, 2014, and June 9, 2015, for patients admitted to an acute opioid detoxification program at Princeton House in suburban New Jersey. Study goals included assessing the prevalence of HIV, HCV, and HBV infections for these patients, the HCV genotype (GT) carried, and the subsequent linkage to care after discharge from the program. The report was published online April 13 in Emerging Infectious Diseases.

Jezperklauzen/ThinkStock

During the screening period, patients representing 10 of New Jersey’s 21 counties were tested for the presence of HCV antibodies. Approximately two-thirds of all study participants (66.6%) were between 17 and 35 years of age. In this important age demographic, 237 patients (41.4%) screened positive for HCV antibodies, and 187 were available for further study.

HCV viral load data were available from 172 patients (92.0%), with approximately one-fifth (18.6%) screening undetectable. The HCV GTs obtained from 102 patients revealed that most (62.7%) were GT1a, followed by GT3 (25.5%). In a very surprising result, all HCV antibody positive patients were also HIV antibody negative, the researchers noted.

Regarding linkage to care, 16 of the patients (8.6%) in the 17- to 35-year-old age group attended outpatient follow-up appointments, with three (1.6%) starting on an oral, direct-acting antiviral treatment regimen. Two of these three patients were nonadherent to their treatment regimens. Two additional patients expressed willingness to accept treatment, but were denied their prescriptions by their insurance providers. None of the other participants returned for continued care.

The authors said that their results indicated a high prevalence of HCV among young suburban heroin users attending an acute detoxification program serving a wide geographic area, suggesting that New Jersey is part of the second wave of HCV infection following that seen in those born from 1946 to 1964. They also highlighted their findings of a GT3 prevalence more than twice the national average, a complete lack of HIV infection in a population known to be susceptible to it, and disappointing linkage to care outcomes.

The authors said that easy-to-use curative therapy should underscore a need for improved linkage to care and treatment of HCV-infected persons who inject drugs as part of an important public health effort to prevent its continued spread.

This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Conflict of interest information was not disclosed.

CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.

Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).

A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.

The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.

Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.

The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.

MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.

Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).

A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.

The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.

Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.

The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.

MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.

Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).

A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.

The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.

Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.

The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.

MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.

[email protected]

On Twitter @mitchelzoler

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

Low vaccination rates in the United States are in large part due to parental and religious objections to this vaccination that can be overcome by better education and support by pediatricians. It’s been demonstrated that physicians encourage the HPV vaccine less strongly than the other adolescent vaccinations such as Tdap and the meningococcal conjugate vaccine¹. In addition, there is a lack of legislation promoting this vaccine. There are only two states and Washington, D.C., that currently have opt-out state mandates for HPV immunization, compared with 46 states plus Washington, D.C., with similar policies for Tdap². The HPV vaccine is safe, efficacious, and has been demonstrated to reduce mortality and morbidity in our population. It is imperative that we, as pediatricians, strongly encourage and provide these vaccinations to our adolescent patients to help protect our community.

The human papillomavirus (HPV) vaccine was approved for girls in 2008 and for boys in 2011³. However, the adoption rate for HPV immunization in the United States has been dismal. Data from 2014 show only 60% of adolescent girls have received at least one HPV vaccine dose, and only 40% have received three doses⁴. The rates for boys are far worse, with 42% of adolescent boys receiving at least one dose, and only 22% receiving three doses⁴.

HPV is currently the most common sexually transmitted infection in the United States, with an estimated 14 million new infections per year³. Of these, approximately 11,000 will progress to cervical cancers and 9,000 to male anogenital cancers each year. Annually there are about 4,000 cervical cancer deaths in the United States3.

Three vaccines are approved by the Food and Drug Administration to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers (as well as oropharyngeal and other anogenital cancers). Gardasil also prevents infection with HPV types 6 and 11, associated with approximately 90% of anogenital warts. Gardasil 9 prevents infection with the same four HPV types plus five other high-risk HPV types (31, 33, 45, 52, and 58); it is called a nonavalent, or 9-valent, vaccine.

The HPV vaccines have the ability to reduce mortality and morbidity in our patients. A study published in the New England Journal of Medicine in 2011 demonstrated that vaccination with the full HPV series in males 16-26 years prior to HPV exposure led to a 90% efficacy in preventing HPV-related disease^5, compared with a 60% efficacy if given after HPV exposure or if the individual received an incomplete dose series.

A recent Pediatrics study reported data since initiation of the vaccination program in American adolescent and young adult women⁶. The data showed a reduction in HPV-related disease of 64% in the 14- to 19-year age group and a reduction of 34% in the older age group (aged 20-24 years). This is impressive given our currently low vaccination rates.

A Lancet meta-analysis shows evidence of herd immunity and cross-protective effects when vaccination rates are greater than 50% in the population⁷. This allows groups that aren’t currently approved for vaccination to have a reduction in disease and allows for some protection against HPV types that aren’t currently covered by the vaccines.

So we pediatricians have a job to do in protecting our patients by encouraging HPV immunization.

References

1. Pediatrics. 2016 Feb;137(2):1-9.

2. www.immunize.org/laws

3. www.cdc.gov/hpv/hcp/clinician-factsheet.html

4. MMWR. 2015;64(29);784-92

5. N Engl J Med. 2011;364(5):401-11.

6. Pediatrics. 2016;137(3):1-9.

7. Lancet Infect Dis. 2015;15(5):565-80.

Dr. Denby is a second-year internal medicine/pediatrics resident at Vanderbilt University Medical Center in Nashville, Tenn.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

A rapid bedside diagnostic test for influenza showed consistent sensitivity and specificity across four consecutive flu seasons in a single pediatric ED in France, according to a report in Diagnostic Microbiology and Infectious Disease.

During flu seasons, it is difficult to distinguish young children who have the flu from those who have serious bacterial infections because clinical symptoms alone cannot differentiate the two conditions and fever may be the only symptom during the onset of a bacterial infection. Rapid influenza diagnostic tests purport to help ED clinicians estimate the probability of influenza at the bedside, which in turn can reduce the need for further diagnostic testing, length of ED stay, inappropriate use of antibiotics, and the costs of care, said Dr. E. Avril of the pediatric ED, University Hospital in Nantes, France, and associates.

©mik38/Fotolia.com

To assess the diagnostic value of one rapid influenza diagnostic test used in this setting every winter, the investigators studied 764 patients younger than age 5 years who were admitted to the ED during four consecutive flu seasons with fever of no known origin. The prevalence of influenza varied widely during the study period, from a low of 30% to a high of 62%.

The rapid diagnostic test performed comparably well across the four flu seasons, with only a modest decrease in sensitivity and specificity during the 2010 H₁N₁ flu pandemic. The bedside test had an overall sensitivity of 0.82, a specificity of 0.98, a positive likelihood ratio of 37.8, and a negative likelihood ratio of 0.19. These results are similar to those of two previous small-scale studies that found sensitivities of 69%-85% and specificities of 83%-98%, Dr. Avril and associates said (Diag Microbiol Infect Dis. 2016 doi:10.1016/j.diagmicrobio.2016.03.015).

These findings “support the rational use of rapid influenza diagnostic tests in clinical practice for young children presenting with fever without a source during flu season,” the investigators said.

Dr. Avril and associates added that they assessed only one rapid diagnostic test for influenza (QuickVue) – the only one available in their ED because of cost – but that there are 22 such tests commercially available. Nantes University Hospital supported the study. Dr. Avril and associates reported having no relevant disclosures.

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.

HOLLYWOOD, FLA. – Current evidence suggests that molecular tests for prostate cancer are prognostic and can help clinicians and patients with difficult treatment decisions. In the not-too-distant future, gene tests could also guide choice of therapies.

“I think that the largest impact is going to come in areas of both the greatest treatment uncertainty and areas where we can be predictive about the response to treatment,” said Dr. Ashley Ross, a urologic oncologist and pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Multigene panels may soon be able help identify which patients might benefit more from radical prostatectomy or radiation therapy, whether radiation therapy effects could be enhanced with the addition of androgen-deprivation therapy, and whether early use of docetaxel might add therapeutic benefit, he said at the annual conference of the National Comprehensive Cancer Network.

The 2016 iteration of the NCCN guidelines for the treatment of prostate cancer include a note stating that “men with clinically localized disease may consider the use of tumor-based molecular assays. Retrospective case cohort studies have shown that molecular assays performed on biopsy or prostatectomy specimens provide prognostic information independent of NCCN risk groups.”

The use of molecular assays may inform treatment decisions by helping to predict the likelihood of death if a patient is managed conservatively, risks for biochemical progression after radical prostatectomy or external beam therapy, and the likelihood that a patient could develop metastatic disease after radical prostatectomy or salvage radiotherapy, the guidelines say.

Dr. Ross reviewed the molecular biology of localized prostate cancer and the benefits and risks of currently available molecular tests.

“We’ve had an increased ability to get molecular information or genomic information from very limited amounts of routinely-stored pathologic tissue, and that’s resulted in the generation of many molecular-based tissue tests in prostate cancer. With the emergence of those tests and a lot of aggressive marketing, there has been a lot of confusion for patients and providers about whether we should use them or not and in what context,” he said.

Prostate cancer is genomically complex, even in the localized stage, with copy number alterations, deletions, and amplifications; chromosomal rearrangements; and point mutations, he said.

One of the best characterized genomic events is the early loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog). This gene works within the PI3 kinase (PI3K)/AKT pathway. PI3K pathway mutations have been identified in up to 40% of all primary prostate cancers and 100% of mutations, Dr. Ross explained.

Loss of PTEN itself has been detected in about 15%-40% of primary prostate cancers and 50% of metastases, and the loss correlates with disease stage and tumor grade.

The NCCN guidelines list six available tissue-based tests for prostate cancer prognosis, including tests based on general cancer features such as cell-cycle proliferation, and those based on specific molecular features of cancer.

An example of the general type of test is the Ki-67 immunohistochemistry (IHC) test, which looks for a cellular marker of proliferation, and has been shown to have independent prognostic significance after radiation therapy or radical prostatectomy. This test is not currently recommended by the Medicare Molecular Diagnostic Services (MolDx) program, however.

Another general-type test is the Polaris quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) panel, which tests for 31 cell-cycle-related genes and 15 “housekeeping” controls. This test is recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy. It has been shown to independently predict prostate cancer–specific mortality, biochemical failure/recurrence, and metastasis, the guidelines say.

Tests based on molecular features include:

• PTEN/ERG, an IHC or fluorescent in situ hybridization test that has been shown to predict prostate cancer–specific mortality, upgrading to Gleason pattern 4 on radical prostatectomy, and biochemical recurrence (not MolDx recommended).

• Decipher, a whole-transcriptome 1.4M RNA expression oligonucleotide microarray shown to predict biochemical failure, metastasis, and prostate cancer–specific mortality (recommended for postradical prostatectomy for patients with pT2 tumors with positive margins, and pT3 disease, and rising PSA above nadir);

• Oncotype DX, an RT-PCR assay for 12 prostate cancer genes and five housekeeping controls (recommended for post-biopsy evaluation of men with very-low-risk or low-risk prostate cancer who at the time of diagnosis have at least 10 years of life expectancy).

• ProMark, multiplex immunofluorescent staining of eight proteins, which has been shown to independently predict non–organ-confined pT3 disease or Gleason pattern 4 disease on radical prostatectomy (not reviewed).

Dr. Ross said that in his practice, he generally does not order molecular testing for surveillance of men older than 65 who have very-low-risk disease. For men with low-risk disease, however, molecular testing may help in clinical decision making to predict upgrading or disease progression.

“There’s limited data from surveillance populations, but these tests can be used in this context with retrospective data available, realizing that in most cases the tests will be confirmative, or another way of thinking about it is ‘noninformative,’ so there are some considerations about cost in that context,” he said. For men with intermediate or high-risk disease, however, currently available tests are not good at predicting what an individual patient’s response would be to a specific type of therapy, whether surgery, radiation, androgen deprivation, chemotherapy, or a combination.

“This is an area where predictive biomarkers would be very informative. There is ongoing research, and I think this is an area of potentially large advancement in how we risk-stratify our patients,” Dr. Ross said.