Because prostate cancer (PCa) is a heterogeneous disease, researchers from Universitat de Barcelona in Spain say that a combination of biomarkers would outperform single markers in detection. In a previous study, they identified new putative mRNA markers for PCa diagnosis, tested some of those biomarkers, and validated the commercially available test based on urine prostate cancer antigen 3 (PCA3 ) expression along with the best-performing mRNA panels of biomarkers reported.

Related:Early-Stage Prostate Cancer Incidence Declines Following USPSTF Guidelines Update

Urine samples collected from 224 men and 10 patients with prostate specific antigen (PSA) levels > 4 were included as controls. Seven of 42 genes that the researchers evaluated were independent predictors for PCa. From these data, the researchers developed a 4-gene expression signature, HIST1H2BG, SPP1, ELF3, and PCA3, with higher diagnostic accuracy than PCA3, the only noninvasive urinary biomarker commercially available. Their 4-gene signature had a sensitivity of 77% and specificity of 67% for discriminating between tumor and control urines and a positive predictive value of 83%.

Related: Prostate Cancer in Seniors, Part 1: Epidemiology, Pathology, and Screening

The researchers say their findings suggest that a urinary biomarker panel could improve detection of PCa.  However, they add that the accuracy of the available urinary panels—including their signature—is not yet high enough to warrant using them routinely.

Related: Prostate Cancer Survivorship Care

Mengual L, Lozano JJ, Ingelmo-Torres M, et al. BMC Cancer. 2016;16(1):76.

Because prostate cancer (PCa) is a heterogeneous disease, researchers from Universitat de Barcelona in Spain say that a combination of biomarkers would outperform single markers in detection. In a previous study, they identified new putative mRNA markers for PCa diagnosis, tested some of those biomarkers, and validated the commercially available test based on urine prostate cancer antigen 3 (PCA3 ) expression along with the best-performing mRNA panels of biomarkers reported.

Related:Early-Stage Prostate Cancer Incidence Declines Following USPSTF Guidelines Update

Urine samples collected from 224 men and 10 patients with prostate specific antigen (PSA) levels > 4 were included as controls. Seven of 42 genes that the researchers evaluated were independent predictors for PCa. From these data, the researchers developed a 4-gene expression signature, HIST1H2BG, SPP1, ELF3, and PCA3, with higher diagnostic accuracy than PCA3, the only noninvasive urinary biomarker commercially available. Their 4-gene signature had a sensitivity of 77% and specificity of 67% for discriminating between tumor and control urines and a positive predictive value of 83%.

Related: Prostate Cancer in Seniors, Part 1: Epidemiology, Pathology, and Screening

The researchers say their findings suggest that a urinary biomarker panel could improve detection of PCa.  However, they add that the accuracy of the available urinary panels—including their signature—is not yet high enough to warrant using them routinely.

Related: Prostate Cancer Survivorship Care

Mengual L, Lozano JJ, Ingelmo-Torres M, et al. BMC Cancer. 2016;16(1):76.

Because prostate cancer (PCa) is a heterogeneous disease, researchers from Universitat de Barcelona in Spain say that a combination of biomarkers would outperform single markers in detection. In a previous study, they identified new putative mRNA markers for PCa diagnosis, tested some of those biomarkers, and validated the commercially available test based on urine prostate cancer antigen 3 (PCA3 ) expression along with the best-performing mRNA panels of biomarkers reported.

Related:Early-Stage Prostate Cancer Incidence Declines Following USPSTF Guidelines Update

Urine samples collected from 224 men and 10 patients with prostate specific antigen (PSA) levels > 4 were included as controls. Seven of 42 genes that the researchers evaluated were independent predictors for PCa. From these data, the researchers developed a 4-gene expression signature, HIST1H2BG, SPP1, ELF3, and PCA3, with higher diagnostic accuracy than PCA3, the only noninvasive urinary biomarker commercially available. Their 4-gene signature had a sensitivity of 77% and specificity of 67% for discriminating between tumor and control urines and a positive predictive value of 83%.

Related: Prostate Cancer in Seniors, Part 1: Epidemiology, Pathology, and Screening

The researchers say their findings suggest that a urinary biomarker panel could improve detection of PCa.  However, they add that the accuracy of the available urinary panels—including their signature—is not yet high enough to warrant using them routinely.

Related: Prostate Cancer Survivorship Care

Mengual L, Lozano JJ, Ingelmo-Torres M, et al. BMC Cancer. 2016;16(1):76.

ATLANTA – Both short and long sleep duration during pregnancy are associated with extremes of gestational weight gain, according to findings from a multicenter prospective cohort study.

Among 760 nulliparous women with a singleton gestation who were part of the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring mothers-to-be) network – a National Institute of Child Health and Human Development cohort of more than 10,000 women – the 2.1% with average sleep duration of fewer than 6 hours and the 5.2% with sleep duration greater than 9 hours had the highest rates of low gestational weight gain (z less than –1). The differences were statistically significant, compared with those with average sleep duration of 7 to fewer than 9 hours, at visits between 16 and 21 weeks and between 22 and 29 weeks (P less than .0001, P = .04, respectively), Dr. Francesca Facco reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

For example, at visit 2, the rate of low gestational weight gain was 18.8% and 35.5% for those with sleep duration fewer than 6 hours and more than 9 hours, respectively, vs. 8.2% for those with sleep duration of 6 to fewer than 7 hours, and 12% for those with 7 to fewer than 8 hours.

The differences were similar in magnitude at the last weight measure prior to delivery but did not reach statistical significance, said Dr. Facco of Magee-Women’s Research Institute, University of Pittsburgh.

“Nonlinear relationships were observed between sleep duration and gestational weight gain,” she said, adding that at all gestational weight gain assessments, high gestational weight gain occurred more frequently as sleep duration shortened.

“We found a U-shaped relationship between sleep and low gestational weight gain; women with the shortest and the longest sleep duration had the highest rates of low gestational weight gain,” she said.

The findings suggest that both long and short sleep duration are associated with extremes of gestational weight gain.

Study subjects were enrolled in the nuMoM2b study and were recruited at the second study visit (16-21 weeks) to wear an actigraph to measure sleep activity for 7 consecutive days. The women, who had a mean age of 27 years, also kept a sleep diary. A little over half (51.5%) were normal weight, 3% were underweight, and 45.5% were overweight or obese. Gestational weight gain was examined using age-standardized z scores, which are a measure of gestational weight gain uncorrelated with gestational age and body mass index.

Sleep is getting more and more attention as an important health behavior, especially in relation to weight and metabolism, Dr. Facco said, noting that short sleep duration has consistently been associated with higher body mass index, and studies show that short sleep duration hinders weight loss efforts.

Data on long sleep duration are less clear but suggest an age-dependent relationship, she said.

The current study was undertaken to evaluate whether the findings in nonpregnant women also apply during pregnancy.

Data from the same cohort, which were presented at the 2015 Pregnancy Meeting, showed that women with sleep duration of fewer than 7 hours had twice the rate of gestational diabetes, compared with those who slept 7 or more hours. The finding remained significant even after adjusting for age and body mass index. Those findings are congruous with the current findings, Dr. Facco said, explaining that the short sleepers were those most likely to have the greatest weight gain, thus putting them at higher risk of gestational diabetes.

“Poor sleep in pregnancy has been linked to adverse pregnancy outcomes, and this association between sleep and gestational weight gain suggests one possible mechanism for this association,” she concluded.

The nuMoM2b study is funded by the National Institutes of Health. Dr. Facco reported having no conflicts of interest.

[email protected]

ATLANTA – Both short and long sleep duration during pregnancy are associated with extremes of gestational weight gain, according to findings from a multicenter prospective cohort study.

Among 760 nulliparous women with a singleton gestation who were part of the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring mothers-to-be) network – a National Institute of Child Health and Human Development cohort of more than 10,000 women – the 2.1% with average sleep duration of fewer than 6 hours and the 5.2% with sleep duration greater than 9 hours had the highest rates of low gestational weight gain (z less than –1). The differences were statistically significant, compared with those with average sleep duration of 7 to fewer than 9 hours, at visits between 16 and 21 weeks and between 22 and 29 weeks (P less than .0001, P = .04, respectively), Dr. Francesca Facco reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

For example, at visit 2, the rate of low gestational weight gain was 18.8% and 35.5% for those with sleep duration fewer than 6 hours and more than 9 hours, respectively, vs. 8.2% for those with sleep duration of 6 to fewer than 7 hours, and 12% for those with 7 to fewer than 8 hours.

The differences were similar in magnitude at the last weight measure prior to delivery but did not reach statistical significance, said Dr. Facco of Magee-Women’s Research Institute, University of Pittsburgh.

“Nonlinear relationships were observed between sleep duration and gestational weight gain,” she said, adding that at all gestational weight gain assessments, high gestational weight gain occurred more frequently as sleep duration shortened.

“We found a U-shaped relationship between sleep and low gestational weight gain; women with the shortest and the longest sleep duration had the highest rates of low gestational weight gain,” she said.

The findings suggest that both long and short sleep duration are associated with extremes of gestational weight gain.

Study subjects were enrolled in the nuMoM2b study and were recruited at the second study visit (16-21 weeks) to wear an actigraph to measure sleep activity for 7 consecutive days. The women, who had a mean age of 27 years, also kept a sleep diary. A little over half (51.5%) were normal weight, 3% were underweight, and 45.5% were overweight or obese. Gestational weight gain was examined using age-standardized z scores, which are a measure of gestational weight gain uncorrelated with gestational age and body mass index.

Sleep is getting more and more attention as an important health behavior, especially in relation to weight and metabolism, Dr. Facco said, noting that short sleep duration has consistently been associated with higher body mass index, and studies show that short sleep duration hinders weight loss efforts.

Data on long sleep duration are less clear but suggest an age-dependent relationship, she said.

The current study was undertaken to evaluate whether the findings in nonpregnant women also apply during pregnancy.

Data from the same cohort, which were presented at the 2015 Pregnancy Meeting, showed that women with sleep duration of fewer than 7 hours had twice the rate of gestational diabetes, compared with those who slept 7 or more hours. The finding remained significant even after adjusting for age and body mass index. Those findings are congruous with the current findings, Dr. Facco said, explaining that the short sleepers were those most likely to have the greatest weight gain, thus putting them at higher risk of gestational diabetes.

“Poor sleep in pregnancy has been linked to adverse pregnancy outcomes, and this association between sleep and gestational weight gain suggests one possible mechanism for this association,” she concluded.

The nuMoM2b study is funded by the National Institutes of Health. Dr. Facco reported having no conflicts of interest.

[email protected]

ATLANTA – Both short and long sleep duration during pregnancy are associated with extremes of gestational weight gain, according to findings from a multicenter prospective cohort study.

Among 760 nulliparous women with a singleton gestation who were part of the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring mothers-to-be) network – a National Institute of Child Health and Human Development cohort of more than 10,000 women – the 2.1% with average sleep duration of fewer than 6 hours and the 5.2% with sleep duration greater than 9 hours had the highest rates of low gestational weight gain (z less than –1). The differences were statistically significant, compared with those with average sleep duration of 7 to fewer than 9 hours, at visits between 16 and 21 weeks and between 22 and 29 weeks (P less than .0001, P = .04, respectively), Dr. Francesca Facco reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

For example, at visit 2, the rate of low gestational weight gain was 18.8% and 35.5% for those with sleep duration fewer than 6 hours and more than 9 hours, respectively, vs. 8.2% for those with sleep duration of 6 to fewer than 7 hours, and 12% for those with 7 to fewer than 8 hours.

The differences were similar in magnitude at the last weight measure prior to delivery but did not reach statistical significance, said Dr. Facco of Magee-Women’s Research Institute, University of Pittsburgh.

“Nonlinear relationships were observed between sleep duration and gestational weight gain,” she said, adding that at all gestational weight gain assessments, high gestational weight gain occurred more frequently as sleep duration shortened.

“We found a U-shaped relationship between sleep and low gestational weight gain; women with the shortest and the longest sleep duration had the highest rates of low gestational weight gain,” she said.

The findings suggest that both long and short sleep duration are associated with extremes of gestational weight gain.

Study subjects were enrolled in the nuMoM2b study and were recruited at the second study visit (16-21 weeks) to wear an actigraph to measure sleep activity for 7 consecutive days. The women, who had a mean age of 27 years, also kept a sleep diary. A little over half (51.5%) were normal weight, 3% were underweight, and 45.5% were overweight or obese. Gestational weight gain was examined using age-standardized z scores, which are a measure of gestational weight gain uncorrelated with gestational age and body mass index.

Sleep is getting more and more attention as an important health behavior, especially in relation to weight and metabolism, Dr. Facco said, noting that short sleep duration has consistently been associated with higher body mass index, and studies show that short sleep duration hinders weight loss efforts.

Data on long sleep duration are less clear but suggest an age-dependent relationship, she said.

The current study was undertaken to evaluate whether the findings in nonpregnant women also apply during pregnancy.

Data from the same cohort, which were presented at the 2015 Pregnancy Meeting, showed that women with sleep duration of fewer than 7 hours had twice the rate of gestational diabetes, compared with those who slept 7 or more hours. The finding remained significant even after adjusting for age and body mass index. Those findings are congruous with the current findings, Dr. Facco said, explaining that the short sleepers were those most likely to have the greatest weight gain, thus putting them at higher risk of gestational diabetes.

“Poor sleep in pregnancy has been linked to adverse pregnancy outcomes, and this association between sleep and gestational weight gain suggests one possible mechanism for this association,” she concluded.

The nuMoM2b study is funded by the National Institutes of Health. Dr. Facco reported having no conflicts of interest.

[email protected]

Compared with women using copper IUDs, women using depot medroxyprogesterone acetate, the contraceptive ring, and the implant were more likely to report a lack of interest in sex in a survey.

Women reporting side effects are twice as likely to discontinue their oral contraceptive pills and subsequently are at risk for unintended pregnancy. Further, sexual side effects have been reported by one in five women taking oral contraceptives, despite research indicating little impact on sex drive in most women taking the drugs. In this study, Dr. Jeffrey Peipert of Washington University, St. Louis, and his colleagues sought to clarify whether there is any association between other forms of hormonal contraception and effects on sexual desire.

Robert Boston/Washington University

The researchers performed a cross-sectional analysis of data from the Contraceptive CHOICE Project 6-month survey. The Contraceptive CHOICE Project was a prospective cohort study of 9,256 women that aimed to promote reversible, long-acting contraceptive methods and lessen barriers to all forms of contraception.

Complete data were available on 1,938 participants who had a mean age of 25 years. Half of the participants were black, 51% were nulliparous, and 59% had never married or were single. The contraception methods used included the levonorgestrel IUD (43%), the subdermal contraceptive implant (23%), the copper IUD (14%), oral contraceptive pills (7%), depot medroxyprogesterone acetate (DMPA) (6%), the contraceptive vaginal ring (5%), and the contraceptive patch (2%).

Overall, 23.9% of the study participants reported lacking interest in sex for several months or more. Women reporting a lack of sexual interest were more likely to be black (odds ratio, 2.23), and living with a partner or married (OR, 1.51). Women who had more children, reported depression or poor health, and had a low socioeconomic status were also more likely to report a lack of interest in sex (Obstet Gynecol. 2016;127:563-72).

When compared with women using the copper IUD, women using DMPA were more likely to report lack of interest in sex at 6 months (adjusted OR, 2.61; 95% confidence interval, 1.47-4.61). Similar trends were seen for the vaginal ring (aOR, 2.53; 95% CI, 1.37-4.69), and the contraceptive implant (aOR, 1.60; 95% CI, 1.03-2.49). Likewise, more women using DMPA reported not finding sex pleasurable than women using the copper IUD (20% versus 11.9%, P = .04).

The researchers found no association between lack of libido and the hormonal IUD, oral contraceptive pill, and contraceptive patch.

“Lack of interest in sex in implant and DMPA users may be related to the hormonal composition of these methods,” the researchers wrote. “The implant and DMPA injection are the only two contraceptive methods included in this study that release progestins systemically. Although there is conflicting evidence concerning a link between progestins and libido, there is some evidence to suggest that estrogens play an essential role in female sexuality.”

The researchers stressed that confirmation of the findings is warranted.

The Contraceptive CHOICE Project was funded by the Susan T. Buffett Foundation and this study was supported by an award from the National Institutes of Health. Dr. Peipert reported research funding from Bayer, Teva, and Merck, and serving on the advisory boards for Teva and Perrigo.

Compared with women using copper IUDs, women using depot medroxyprogesterone acetate, the contraceptive ring, and the implant were more likely to report a lack of interest in sex in a survey.

Women reporting side effects are twice as likely to discontinue their oral contraceptive pills and subsequently are at risk for unintended pregnancy. Further, sexual side effects have been reported by one in five women taking oral contraceptives, despite research indicating little impact on sex drive in most women taking the drugs. In this study, Dr. Jeffrey Peipert of Washington University, St. Louis, and his colleagues sought to clarify whether there is any association between other forms of hormonal contraception and effects on sexual desire.

Robert Boston/Washington University

The researchers performed a cross-sectional analysis of data from the Contraceptive CHOICE Project 6-month survey. The Contraceptive CHOICE Project was a prospective cohort study of 9,256 women that aimed to promote reversible, long-acting contraceptive methods and lessen barriers to all forms of contraception.

Complete data were available on 1,938 participants who had a mean age of 25 years. Half of the participants were black, 51% were nulliparous, and 59% had never married or were single. The contraception methods used included the levonorgestrel IUD (43%), the subdermal contraceptive implant (23%), the copper IUD (14%), oral contraceptive pills (7%), depot medroxyprogesterone acetate (DMPA) (6%), the contraceptive vaginal ring (5%), and the contraceptive patch (2%).

Overall, 23.9% of the study participants reported lacking interest in sex for several months or more. Women reporting a lack of sexual interest were more likely to be black (odds ratio, 2.23), and living with a partner or married (OR, 1.51). Women who had more children, reported depression or poor health, and had a low socioeconomic status were also more likely to report a lack of interest in sex (Obstet Gynecol. 2016;127:563-72).

When compared with women using the copper IUD, women using DMPA were more likely to report lack of interest in sex at 6 months (adjusted OR, 2.61; 95% confidence interval, 1.47-4.61). Similar trends were seen for the vaginal ring (aOR, 2.53; 95% CI, 1.37-4.69), and the contraceptive implant (aOR, 1.60; 95% CI, 1.03-2.49). Likewise, more women using DMPA reported not finding sex pleasurable than women using the copper IUD (20% versus 11.9%, P = .04).

The researchers found no association between lack of libido and the hormonal IUD, oral contraceptive pill, and contraceptive patch.

“Lack of interest in sex in implant and DMPA users may be related to the hormonal composition of these methods,” the researchers wrote. “The implant and DMPA injection are the only two contraceptive methods included in this study that release progestins systemically. Although there is conflicting evidence concerning a link between progestins and libido, there is some evidence to suggest that estrogens play an essential role in female sexuality.”

The researchers stressed that confirmation of the findings is warranted.

The Contraceptive CHOICE Project was funded by the Susan T. Buffett Foundation and this study was supported by an award from the National Institutes of Health. Dr. Peipert reported research funding from Bayer, Teva, and Merck, and serving on the advisory boards for Teva and Perrigo.

Compared with women using copper IUDs, women using depot medroxyprogesterone acetate, the contraceptive ring, and the implant were more likely to report a lack of interest in sex in a survey.

Women reporting side effects are twice as likely to discontinue their oral contraceptive pills and subsequently are at risk for unintended pregnancy. Further, sexual side effects have been reported by one in five women taking oral contraceptives, despite research indicating little impact on sex drive in most women taking the drugs. In this study, Dr. Jeffrey Peipert of Washington University, St. Louis, and his colleagues sought to clarify whether there is any association between other forms of hormonal contraception and effects on sexual desire.

Robert Boston/Washington University

The researchers performed a cross-sectional analysis of data from the Contraceptive CHOICE Project 6-month survey. The Contraceptive CHOICE Project was a prospective cohort study of 9,256 women that aimed to promote reversible, long-acting contraceptive methods and lessen barriers to all forms of contraception.

Complete data were available on 1,938 participants who had a mean age of 25 years. Half of the participants were black, 51% were nulliparous, and 59% had never married or were single. The contraception methods used included the levonorgestrel IUD (43%), the subdermal contraceptive implant (23%), the copper IUD (14%), oral contraceptive pills (7%), depot medroxyprogesterone acetate (DMPA) (6%), the contraceptive vaginal ring (5%), and the contraceptive patch (2%).

Overall, 23.9% of the study participants reported lacking interest in sex for several months or more. Women reporting a lack of sexual interest were more likely to be black (odds ratio, 2.23), and living with a partner or married (OR, 1.51). Women who had more children, reported depression or poor health, and had a low socioeconomic status were also more likely to report a lack of interest in sex (Obstet Gynecol. 2016;127:563-72).

When compared with women using the copper IUD, women using DMPA were more likely to report lack of interest in sex at 6 months (adjusted OR, 2.61; 95% confidence interval, 1.47-4.61). Similar trends were seen for the vaginal ring (aOR, 2.53; 95% CI, 1.37-4.69), and the contraceptive implant (aOR, 1.60; 95% CI, 1.03-2.49). Likewise, more women using DMPA reported not finding sex pleasurable than women using the copper IUD (20% versus 11.9%, P = .04).

The researchers found no association between lack of libido and the hormonal IUD, oral contraceptive pill, and contraceptive patch.

“Lack of interest in sex in implant and DMPA users may be related to the hormonal composition of these methods,” the researchers wrote. “The implant and DMPA injection are the only two contraceptive methods included in this study that release progestins systemically. Although there is conflicting evidence concerning a link between progestins and libido, there is some evidence to suggest that estrogens play an essential role in female sexuality.”

The researchers stressed that confirmation of the findings is warranted.

The Contraceptive CHOICE Project was funded by the Susan T. Buffett Foundation and this study was supported by an award from the National Institutes of Health. Dr. Peipert reported research funding from Bayer, Teva, and Merck, and serving on the advisory boards for Teva and Perrigo.

The findings of a recent Cochrane review back up guidelines that recommend NSAIDs as an appropriate first-line treatment for people with axial spondyloarthritis (axSpA).

NSAIDs have been associated with a variety of gastrointestinal effects and an increased risk of cardiovascular events, heart failure, and renal toxicity, an international team of researchers led by Dr. Féline P.B. Kroon of the Leiden University Medical Center in the Netherlands noted in the review, published in the Journal of Rheumatology.

Denise Fulton/Frontline Medical News

“It is therefore crucial to know whether the benefits offset the risks, especially because the therapy is often given for extended periods of time,” the researchers wrote in background information to the article (J Rheumatol. 2016. doi: 10.3899/jrheum.150721).

The investigators analyzed the evidence to assess the benefits and harms of NSAIDs in controlling symptoms, disease activity, and radiographic progression in patients with axSpA.

Reviewing 29 randomized, controlled trials and two “quasi” RCT studies in a pooled analyses, the research team found that, compared with placebo, both traditional and cyclooxygenase-2 (COX-2) NSAIDs were consistently more efficacious at 6 weeks and equally safe after 12 weeks.

The researchers also observed no significant differences in benefits or harms between the two NSAID classes. An increased number of neurologic events were initially observed for indomethacin, but the finding was not statistically significant when studies with high or unclear risk of bias were excluded.

Two single studies included in the review also suggested NSAIDs might retard radiographic progression in the spine in axSpA, especially in certain subgroups of patients such as those with high C-reactive protein. Although this would most likely be best achieved by continuous rather than on-demand use, the researchers said.

“The results of the review are in keeping with current recommendations that NSAIDs are appropriate first-line treatments of patients with axSpA with active disease before tumor necrosis factor inhibitor biologicals are applied,” they concluded.

However, they said it was surprising that they were unable to confirm the safety concerns associated with traditional NSAIDs and COX-2 NSAIDs.

This finding could mean that short-term use of either class of NSAID in this population of patients is not associated with an increased risk of GI or other adverse events.

But it could also be because most patients with ankylosing spondylitis are younger and have fewer comorbidities than patients with other rheumatic diseases.

The finding that people with ankylosing spondylitis have fewer adverse events with biologics, compared with patients with other rheumatic diseases, supported this theory, they said.

“It is technically still possible that lack of statistical power is at the basis of this, but we feel it is more likely that in the studied population and within the studied time frame (i.e., short-term), the risks of GI or cardiovascular toxicity are really not increased,” they wrote.

The review had several limitations, including that many trials were older (61% of the included studies were published before 1990) and there were not sufficient data to draw conclusions on long-term safety.

The findings of a recent Cochrane review back up guidelines that recommend NSAIDs as an appropriate first-line treatment for people with axial spondyloarthritis (axSpA).

NSAIDs have been associated with a variety of gastrointestinal effects and an increased risk of cardiovascular events, heart failure, and renal toxicity, an international team of researchers led by Dr. Féline P.B. Kroon of the Leiden University Medical Center in the Netherlands noted in the review, published in the Journal of Rheumatology.

Denise Fulton/Frontline Medical News

“It is therefore crucial to know whether the benefits offset the risks, especially because the therapy is often given for extended periods of time,” the researchers wrote in background information to the article (J Rheumatol. 2016. doi: 10.3899/jrheum.150721).

The investigators analyzed the evidence to assess the benefits and harms of NSAIDs in controlling symptoms, disease activity, and radiographic progression in patients with axSpA.

Reviewing 29 randomized, controlled trials and two “quasi” RCT studies in a pooled analyses, the research team found that, compared with placebo, both traditional and cyclooxygenase-2 (COX-2) NSAIDs were consistently more efficacious at 6 weeks and equally safe after 12 weeks.

The researchers also observed no significant differences in benefits or harms between the two NSAID classes. An increased number of neurologic events were initially observed for indomethacin, but the finding was not statistically significant when studies with high or unclear risk of bias were excluded.

Two single studies included in the review also suggested NSAIDs might retard radiographic progression in the spine in axSpA, especially in certain subgroups of patients such as those with high C-reactive protein. Although this would most likely be best achieved by continuous rather than on-demand use, the researchers said.

“The results of the review are in keeping with current recommendations that NSAIDs are appropriate first-line treatments of patients with axSpA with active disease before tumor necrosis factor inhibitor biologicals are applied,” they concluded.

However, they said it was surprising that they were unable to confirm the safety concerns associated with traditional NSAIDs and COX-2 NSAIDs.

This finding could mean that short-term use of either class of NSAID in this population of patients is not associated with an increased risk of GI or other adverse events.

But it could also be because most patients with ankylosing spondylitis are younger and have fewer comorbidities than patients with other rheumatic diseases.

The finding that people with ankylosing spondylitis have fewer adverse events with biologics, compared with patients with other rheumatic diseases, supported this theory, they said.

“It is technically still possible that lack of statistical power is at the basis of this, but we feel it is more likely that in the studied population and within the studied time frame (i.e., short-term), the risks of GI or cardiovascular toxicity are really not increased,” they wrote.

The review had several limitations, including that many trials were older (61% of the included studies were published before 1990) and there were not sufficient data to draw conclusions on long-term safety.

The findings of a recent Cochrane review back up guidelines that recommend NSAIDs as an appropriate first-line treatment for people with axial spondyloarthritis (axSpA).

NSAIDs have been associated with a variety of gastrointestinal effects and an increased risk of cardiovascular events, heart failure, and renal toxicity, an international team of researchers led by Dr. Féline P.B. Kroon of the Leiden University Medical Center in the Netherlands noted in the review, published in the Journal of Rheumatology.

Denise Fulton/Frontline Medical News

“It is therefore crucial to know whether the benefits offset the risks, especially because the therapy is often given for extended periods of time,” the researchers wrote in background information to the article (J Rheumatol. 2016. doi: 10.3899/jrheum.150721).

The investigators analyzed the evidence to assess the benefits and harms of NSAIDs in controlling symptoms, disease activity, and radiographic progression in patients with axSpA.

Reviewing 29 randomized, controlled trials and two “quasi” RCT studies in a pooled analyses, the research team found that, compared with placebo, both traditional and cyclooxygenase-2 (COX-2) NSAIDs were consistently more efficacious at 6 weeks and equally safe after 12 weeks.

The researchers also observed no significant differences in benefits or harms between the two NSAID classes. An increased number of neurologic events were initially observed for indomethacin, but the finding was not statistically significant when studies with high or unclear risk of bias were excluded.

Two single studies included in the review also suggested NSAIDs might retard radiographic progression in the spine in axSpA, especially in certain subgroups of patients such as those with high C-reactive protein. Although this would most likely be best achieved by continuous rather than on-demand use, the researchers said.

“The results of the review are in keeping with current recommendations that NSAIDs are appropriate first-line treatments of patients with axSpA with active disease before tumor necrosis factor inhibitor biologicals are applied,” they concluded.

However, they said it was surprising that they were unable to confirm the safety concerns associated with traditional NSAIDs and COX-2 NSAIDs.

This finding could mean that short-term use of either class of NSAID in this population of patients is not associated with an increased risk of GI or other adverse events.

But it could also be because most patients with ankylosing spondylitis are younger and have fewer comorbidities than patients with other rheumatic diseases.

The finding that people with ankylosing spondylitis have fewer adverse events with biologics, compared with patients with other rheumatic diseases, supported this theory, they said.

“It is technically still possible that lack of statistical power is at the basis of this, but we feel it is more likely that in the studied population and within the studied time frame (i.e., short-term), the risks of GI or cardiovascular toxicity are really not increased,” they wrote.

The review had several limitations, including that many trials were older (61% of the included studies were published before 1990) and there were not sufficient data to draw conclusions on long-term safety.

Twenty years ago, Robert Wachter, MD, MHM, and Lee Goldman, MD, first coined the term “hospitalist” in the New England Journal of Medicine.1 A new medical specialty was born along with a new career path dedicated to promoting exceptional care for hospitalized patients.

This year ushers in a new era in medicine. The Society of Hospital Medicine (SHM), the professional medical society representing hospital medicine professionals, is proud to introduce 2016 as the “Year of the Hospitalist … Celebrating 20 Years of Hospital Medicine and Looking to the Future.”

At the 20th anniversary of the term “hospitalist,” SHM remains committed to its mission to transform healthcare and revolutionize patient care by providing members with evidence-based quality improvement and clinical resources, best practices for managing hospital medicine groups (HMGs), and an extensive network of professionals. SHM remains committed to empowering members to lead change, develop the best HM programs, and provide the best patient care.

Help us celebrate by:

• Posting, tweeting, and sharing your SHM and hospital medicine success stories using the hashtag #SHeMpowered on your favorite social media outlets. Express how you are making an impact on patient care via hospital medicine in the YOTH and beyond.
• Visiting and sharing the Future of Hospital Medicine website (futureofhospitalmedicine.org) to learn about the wide variety of resources SHM offers to help medical students and residents navigate and understand hospital medicine and the career options available in the field.

Stay tuned throughout 2016 for regular updates on how SHM is making a difference in healthcare today, how it has changed the face of the specialty, and how you can join in the YOTH celebrations. TH

Brett Radler is SHM’s communications coordinator.

Reference

Wachter RM, Goldman L. The emerging role of “hospitalists” in the American health care system. N Engl J Med. 1996;335:514-517. doi: 10.1056/NEJM199608153350713

Twenty years ago, Robert Wachter, MD, MHM, and Lee Goldman, MD, first coined the term “hospitalist” in the New England Journal of Medicine.1 A new medical specialty was born along with a new career path dedicated to promoting exceptional care for hospitalized patients.

This year ushers in a new era in medicine. The Society of Hospital Medicine (SHM), the professional medical society representing hospital medicine professionals, is proud to introduce 2016 as the “Year of the Hospitalist … Celebrating 20 Years of Hospital Medicine and Looking to the Future.”

At the 20th anniversary of the term “hospitalist,” SHM remains committed to its mission to transform healthcare and revolutionize patient care by providing members with evidence-based quality improvement and clinical resources, best practices for managing hospital medicine groups (HMGs), and an extensive network of professionals. SHM remains committed to empowering members to lead change, develop the best HM programs, and provide the best patient care.

Help us celebrate by:

• Posting, tweeting, and sharing your SHM and hospital medicine success stories using the hashtag #SHeMpowered on your favorite social media outlets. Express how you are making an impact on patient care via hospital medicine in the YOTH and beyond.
• Visiting and sharing the Future of Hospital Medicine website (futureofhospitalmedicine.org) to learn about the wide variety of resources SHM offers to help medical students and residents navigate and understand hospital medicine and the career options available in the field.

Stay tuned throughout 2016 for regular updates on how SHM is making a difference in healthcare today, how it has changed the face of the specialty, and how you can join in the YOTH celebrations. TH

Brett Radler is SHM’s communications coordinator.

Reference

Wachter RM, Goldman L. The emerging role of “hospitalists” in the American health care system. N Engl J Med. 1996;335:514-517. doi: 10.1056/NEJM199608153350713

Twenty years ago, Robert Wachter, MD, MHM, and Lee Goldman, MD, first coined the term “hospitalist” in the New England Journal of Medicine.1 A new medical specialty was born along with a new career path dedicated to promoting exceptional care for hospitalized patients.

This year ushers in a new era in medicine. The Society of Hospital Medicine (SHM), the professional medical society representing hospital medicine professionals, is proud to introduce 2016 as the “Year of the Hospitalist … Celebrating 20 Years of Hospital Medicine and Looking to the Future.”

At the 20th anniversary of the term “hospitalist,” SHM remains committed to its mission to transform healthcare and revolutionize patient care by providing members with evidence-based quality improvement and clinical resources, best practices for managing hospital medicine groups (HMGs), and an extensive network of professionals. SHM remains committed to empowering members to lead change, develop the best HM programs, and provide the best patient care.

Help us celebrate by:

• Posting, tweeting, and sharing your SHM and hospital medicine success stories using the hashtag #SHeMpowered on your favorite social media outlets. Express how you are making an impact on patient care via hospital medicine in the YOTH and beyond.
• Visiting and sharing the Future of Hospital Medicine website (futureofhospitalmedicine.org) to learn about the wide variety of resources SHM offers to help medical students and residents navigate and understand hospital medicine and the career options available in the field.

Stay tuned throughout 2016 for regular updates on how SHM is making a difference in healthcare today, how it has changed the face of the specialty, and how you can join in the YOTH celebrations. TH

Brett Radler is SHM’s communications coordinator.

Reference

Wachter RM, Goldman L. The emerging role of “hospitalists” in the American health care system. N Engl J Med. 1996;335:514-517. doi: 10.1056/NEJM199608153350713

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

Genome testing

Photo courtesy of NIGMS

Researchers say they have identified 3 genetic variants that may double the risk of venous thromboembolism (VTE) in African Americans.

The variants are single-nucleotide polymorphisms (SNPs) found on chromosome 20—rs2144940, rs2567617, and rs1998081.

The study suggests more than a third of African Americans may have at least 1 of these SNPs, but they are much less common among people of Asian or European descent.

Minoli Perera, PharmD, PhD, of the University of Chicago in Illinois, and her colleagues conducted this research and reported the results in Blood.

Dr Perera’s team noted that African Americans are 30% to 60% more likely to suffer from VTE than any other US population. However, well-known genetic risk factors for VTE, such as factor V Leiden, are common in Caucasians but occur infrequently in African Americans.

This realization led the researchers to hypothesize that there might be undiscovered genetic variants more specific to African Americans.

“While African Americans have a high risk for VTE, previous studies have not specifically focused on this population,” Dr Perera said. “If we are not looking for the correct genetic mutations when we run a laboratory test, we are doing a disservice to minority populations.”

To understand the genetic risk factors for VTE specific to African Americans, Dr Perera and her colleagues conducted a genome-wide association study in which they genotyped DNA samples from 578 African Americans, 146 of whom had a history of unprovoked VTE.

The team then confirmed the variants deemed highly prevalent in the first group by genotyping the DNA of an additional group of 159 African Americans, including 94 with VTE.

These analyses suggested a link between VTE and 3 SNPs in chromosome 20, which is associated with decreased expression of thrombomodulin—rs2144940, rs2567617, and rs1998081.

The researchers said the presence of 1 of these 3 SNPs doubles the risk of VTE. In the discovery cohort, the odds ratio was 2.18 for rs2144940, 2.17 for rs2567617, and 2.28 for rs1998081.

In the replication cohort, the odds ratio was 1.89 for rs2144940 and 1.94 for rs1998081. The researchers were not able to test for rs2567617 in this cohort due to high linkage disequilibrium.

The team said their data suggest approximately 36% of African Americans have at least 1 of the 3 SNPs. But the variants were found in much lower frequencies in other ethnicities from previous studies.

“This study not only brings us closer to understanding the cause of VTE in African Americans, it demonstrates the importance of conducting population-specific research in precision medicine,” Dr Perera said.

“Our next steps will involve investigating the predictiveness of these risk factors for VTE with the goal of reducing the high prevalence and burden of VTE in this disproportionately affected population.”

Genome testing

Photo courtesy of NIGMS

Researchers say they have identified 3 genetic variants that may double the risk of venous thromboembolism (VTE) in African Americans.

The variants are single-nucleotide polymorphisms (SNPs) found on chromosome 20—rs2144940, rs2567617, and rs1998081.

The study suggests more than a third of African Americans may have at least 1 of these SNPs, but they are much less common among people of Asian or European descent.

Minoli Perera, PharmD, PhD, of the University of Chicago in Illinois, and her colleagues conducted this research and reported the results in Blood.

Dr Perera’s team noted that African Americans are 30% to 60% more likely to suffer from VTE than any other US population. However, well-known genetic risk factors for VTE, such as factor V Leiden, are common in Caucasians but occur infrequently in African Americans.

This realization led the researchers to hypothesize that there might be undiscovered genetic variants more specific to African Americans.

“While African Americans have a high risk for VTE, previous studies have not specifically focused on this population,” Dr Perera said. “If we are not looking for the correct genetic mutations when we run a laboratory test, we are doing a disservice to minority populations.”

To understand the genetic risk factors for VTE specific to African Americans, Dr Perera and her colleagues conducted a genome-wide association study in which they genotyped DNA samples from 578 African Americans, 146 of whom had a history of unprovoked VTE.

The team then confirmed the variants deemed highly prevalent in the first group by genotyping the DNA of an additional group of 159 African Americans, including 94 with VTE.

These analyses suggested a link between VTE and 3 SNPs in chromosome 20, which is associated with decreased expression of thrombomodulin—rs2144940, rs2567617, and rs1998081.

The researchers said the presence of 1 of these 3 SNPs doubles the risk of VTE. In the discovery cohort, the odds ratio was 2.18 for rs2144940, 2.17 for rs2567617, and 2.28 for rs1998081.

In the replication cohort, the odds ratio was 1.89 for rs2144940 and 1.94 for rs1998081. The researchers were not able to test for rs2567617 in this cohort due to high linkage disequilibrium.

The team said their data suggest approximately 36% of African Americans have at least 1 of the 3 SNPs. But the variants were found in much lower frequencies in other ethnicities from previous studies.

“This study not only brings us closer to understanding the cause of VTE in African Americans, it demonstrates the importance of conducting population-specific research in precision medicine,” Dr Perera said.

“Our next steps will involve investigating the predictiveness of these risk factors for VTE with the goal of reducing the high prevalence and burden of VTE in this disproportionately affected population.”

Genome testing

Photo courtesy of NIGMS

Researchers say they have identified 3 genetic variants that may double the risk of venous thromboembolism (VTE) in African Americans.

The variants are single-nucleotide polymorphisms (SNPs) found on chromosome 20—rs2144940, rs2567617, and rs1998081.

The study suggests more than a third of African Americans may have at least 1 of these SNPs, but they are much less common among people of Asian or European descent.

Minoli Perera, PharmD, PhD, of the University of Chicago in Illinois, and her colleagues conducted this research and reported the results in Blood.

Dr Perera’s team noted that African Americans are 30% to 60% more likely to suffer from VTE than any other US population. However, well-known genetic risk factors for VTE, such as factor V Leiden, are common in Caucasians but occur infrequently in African Americans.

This realization led the researchers to hypothesize that there might be undiscovered genetic variants more specific to African Americans.

“While African Americans have a high risk for VTE, previous studies have not specifically focused on this population,” Dr Perera said. “If we are not looking for the correct genetic mutations when we run a laboratory test, we are doing a disservice to minority populations.”

To understand the genetic risk factors for VTE specific to African Americans, Dr Perera and her colleagues conducted a genome-wide association study in which they genotyped DNA samples from 578 African Americans, 146 of whom had a history of unprovoked VTE.

The team then confirmed the variants deemed highly prevalent in the first group by genotyping the DNA of an additional group of 159 African Americans, including 94 with VTE.

These analyses suggested a link between VTE and 3 SNPs in chromosome 20, which is associated with decreased expression of thrombomodulin—rs2144940, rs2567617, and rs1998081.

The researchers said the presence of 1 of these 3 SNPs doubles the risk of VTE. In the discovery cohort, the odds ratio was 2.18 for rs2144940, 2.17 for rs2567617, and 2.28 for rs1998081.

In the replication cohort, the odds ratio was 1.89 for rs2144940 and 1.94 for rs1998081. The researchers were not able to test for rs2567617 in this cohort due to high linkage disequilibrium.

The team said their data suggest approximately 36% of African Americans have at least 1 of the 3 SNPs. But the variants were found in much lower frequencies in other ethnicities from previous studies.

“This study not only brings us closer to understanding the cause of VTE in African Americans, it demonstrates the importance of conducting population-specific research in precision medicine,” Dr Perera said.

“Our next steps will involve investigating the predictiveness of these risk factors for VTE with the goal of reducing the high prevalence and burden of VTE in this disproportionately affected population.”

CML cells

Image by Difu Wu

Preclinical research suggests chronic myeloid leukemia (CML) patients have a heterogeneous population of long-term hematopoietic stem cells (LTHSCs)—some that can initiate leukemia and some that cannot.

Researchers found they could identify the leukemia-initiating cells by measuring expression of the thrombopoietin receptor MPL. Cells with high MPL expression could initiate CML in mice.

The team said these results suggest the leukemic LTHSCs are the cells responsible for relapse in CML.

“This shows that not all leukemia stem cells are equal,” said study author Ravi Bhatia, MD, of the University of Alabama Birmingham.

“Some are more prone to causing leukemia and relapses, while some others may just hang around without potential for contributing to relapse.”

Dr Bhatia and his colleagues reported these findings in The Journal of Clinical Investigation.

In their experiments, the team used an inducible transgenic mouse model of CML, where the BCR-ABL gene fusion is under the control of a tetracycline-regulated enhancer. This model creates a chronic myeloproliferative disorder that resembles chronic phase CML.

Previous work had shown that only cells with an LTHSC phenotype were capable of long-term repopulation and leukemia-initiating capacity after transplantation to another mouse.

When the researchers transplanted LTHSCs from CML-model mice to other mice, 11 of 20 recipients developed CML, and 9 of 20 showed engraftment with CML cells but did not develop the leukocytosis characteristic of leukemia.

When the LTHSCs from the primary-recipient mice were transferred to secondary recipients, 7 of 17 mice receiving cells from leukemic mice developed CML, and none of the secondary-recipient mice receiving cells from the non-leukemic mice developed CML.

The researchers tested these 2 groups of LTHSCs for differences in gene expression. They found significant differences between the leukemic and non-leukemic LTHSCs for the genes Mpl, c-Myc, CD47, Pten, Sirt1, Ptch1, and Tie2.

The team then decided to focus on Mpl. They used flow cytometry to select LTHSCs with either high or low Mpl expression from CML-model BCR-ABL mice.

Seven of 16 mice receiving Mpl-Hi LTHSCs developed leukemia after transplantation, compared with 1 of 17 receiving Mpl-Lo LTHSCs. This suggested an increased leukemogenic capacity for the Mpl-Hi LTHSCs.

The researchers also investigated the impact of cell-cycle status. They found that CML Mpl-Hi LTHSCs that were in a resting stage of the cell cycle had enhanced long-term engraftment and leukemogenic capacity compared with cycling Mpl-Hi LTHSCs.

The team used virus vectors and shRNA to create Mpl knockdown BCR-ABL LTHSCs and showed that the knockdown cells had a greatly reduced ability to produce leukemia in recipient mice.

The Mpl knockdown cells, after stimulation by the Mpl ligand thrombopoietin, also had reduced expression of the activated transcription factors p-STAT3 and p-STAT5, compared with controls.

Finally, the researchers examined human CML cells for differences between MPL-Hi LTHSCs and MPL-Lo LTHSCs. The results were similar to those observed in mice.

The human MPL-Hi LTHSCs had a higher rate of engraftment than the human MPL-Lo LTHSCs, as tested in a xenograft model using immunodeficient mice.

Additionally, the human MPL-Hi LTHSCs had reduced sensitivity to nilotinib compared with MPL-Lo LTHSCs. However, a Jak/STAT inhibitor significantly reduced cell growth and increased apoptosis in human MPL-Hi LTHSCs.

The researchers concluded that MPL expression is a marker and key regulator of leukemogenic potential and drug sensitivity of CML LTHSCs. They said their findings support further investigation of approaches to antagonize MPL signaling as a potential therapeutic strategy to eliminate leukemia-initiating LTHSCs.

CML cells

Image by Difu Wu

Preclinical research suggests chronic myeloid leukemia (CML) patients have a heterogeneous population of long-term hematopoietic stem cells (LTHSCs)—some that can initiate leukemia and some that cannot.

Researchers found they could identify the leukemia-initiating cells by measuring expression of the thrombopoietin receptor MPL. Cells with high MPL expression could initiate CML in mice.

The team said these results suggest the leukemic LTHSCs are the cells responsible for relapse in CML.

“This shows that not all leukemia stem cells are equal,” said study author Ravi Bhatia, MD, of the University of Alabama Birmingham.

“Some are more prone to causing leukemia and relapses, while some others may just hang around without potential for contributing to relapse.”

Dr Bhatia and his colleagues reported these findings in The Journal of Clinical Investigation.

In their experiments, the team used an inducible transgenic mouse model of CML, where the BCR-ABL gene fusion is under the control of a tetracycline-regulated enhancer. This model creates a chronic myeloproliferative disorder that resembles chronic phase CML.

Previous work had shown that only cells with an LTHSC phenotype were capable of long-term repopulation and leukemia-initiating capacity after transplantation to another mouse.

When the researchers transplanted LTHSCs from CML-model mice to other mice, 11 of 20 recipients developed CML, and 9 of 20 showed engraftment with CML cells but did not develop the leukocytosis characteristic of leukemia.

When the LTHSCs from the primary-recipient mice were transferred to secondary recipients, 7 of 17 mice receiving cells from leukemic mice developed CML, and none of the secondary-recipient mice receiving cells from the non-leukemic mice developed CML.

The researchers tested these 2 groups of LTHSCs for differences in gene expression. They found significant differences between the leukemic and non-leukemic LTHSCs for the genes Mpl, c-Myc, CD47, Pten, Sirt1, Ptch1, and Tie2.

The team then decided to focus on Mpl. They used flow cytometry to select LTHSCs with either high or low Mpl expression from CML-model BCR-ABL mice.

Seven of 16 mice receiving Mpl-Hi LTHSCs developed leukemia after transplantation, compared with 1 of 17 receiving Mpl-Lo LTHSCs. This suggested an increased leukemogenic capacity for the Mpl-Hi LTHSCs.

The researchers also investigated the impact of cell-cycle status. They found that CML Mpl-Hi LTHSCs that were in a resting stage of the cell cycle had enhanced long-term engraftment and leukemogenic capacity compared with cycling Mpl-Hi LTHSCs.

The team used virus vectors and shRNA to create Mpl knockdown BCR-ABL LTHSCs and showed that the knockdown cells had a greatly reduced ability to produce leukemia in recipient mice.

The Mpl knockdown cells, after stimulation by the Mpl ligand thrombopoietin, also had reduced expression of the activated transcription factors p-STAT3 and p-STAT5, compared with controls.

Finally, the researchers examined human CML cells for differences between MPL-Hi LTHSCs and MPL-Lo LTHSCs. The results were similar to those observed in mice.

The human MPL-Hi LTHSCs had a higher rate of engraftment than the human MPL-Lo LTHSCs, as tested in a xenograft model using immunodeficient mice.

Additionally, the human MPL-Hi LTHSCs had reduced sensitivity to nilotinib compared with MPL-Lo LTHSCs. However, a Jak/STAT inhibitor significantly reduced cell growth and increased apoptosis in human MPL-Hi LTHSCs.

The researchers concluded that MPL expression is a marker and key regulator of leukemogenic potential and drug sensitivity of CML LTHSCs. They said their findings support further investigation of approaches to antagonize MPL signaling as a potential therapeutic strategy to eliminate leukemia-initiating LTHSCs.

CML cells

Image by Difu Wu

Preclinical research suggests chronic myeloid leukemia (CML) patients have a heterogeneous population of long-term hematopoietic stem cells (LTHSCs)—some that can initiate leukemia and some that cannot.

Researchers found they could identify the leukemia-initiating cells by measuring expression of the thrombopoietin receptor MPL. Cells with high MPL expression could initiate CML in mice.

The team said these results suggest the leukemic LTHSCs are the cells responsible for relapse in CML.

“This shows that not all leukemia stem cells are equal,” said study author Ravi Bhatia, MD, of the University of Alabama Birmingham.

“Some are more prone to causing leukemia and relapses, while some others may just hang around without potential for contributing to relapse.”

Dr Bhatia and his colleagues reported these findings in The Journal of Clinical Investigation.

In their experiments, the team used an inducible transgenic mouse model of CML, where the BCR-ABL gene fusion is under the control of a tetracycline-regulated enhancer. This model creates a chronic myeloproliferative disorder that resembles chronic phase CML.

Previous work had shown that only cells with an LTHSC phenotype were capable of long-term repopulation and leukemia-initiating capacity after transplantation to another mouse.

When the researchers transplanted LTHSCs from CML-model mice to other mice, 11 of 20 recipients developed CML, and 9 of 20 showed engraftment with CML cells but did not develop the leukocytosis characteristic of leukemia.

When the LTHSCs from the primary-recipient mice were transferred to secondary recipients, 7 of 17 mice receiving cells from leukemic mice developed CML, and none of the secondary-recipient mice receiving cells from the non-leukemic mice developed CML.

The researchers tested these 2 groups of LTHSCs for differences in gene expression. They found significant differences between the leukemic and non-leukemic LTHSCs for the genes Mpl, c-Myc, CD47, Pten, Sirt1, Ptch1, and Tie2.

The team then decided to focus on Mpl. They used flow cytometry to select LTHSCs with either high or low Mpl expression from CML-model BCR-ABL mice.

Seven of 16 mice receiving Mpl-Hi LTHSCs developed leukemia after transplantation, compared with 1 of 17 receiving Mpl-Lo LTHSCs. This suggested an increased leukemogenic capacity for the Mpl-Hi LTHSCs.

The researchers also investigated the impact of cell-cycle status. They found that CML Mpl-Hi LTHSCs that were in a resting stage of the cell cycle had enhanced long-term engraftment and leukemogenic capacity compared with cycling Mpl-Hi LTHSCs.

The team used virus vectors and shRNA to create Mpl knockdown BCR-ABL LTHSCs and showed that the knockdown cells had a greatly reduced ability to produce leukemia in recipient mice.

The Mpl knockdown cells, after stimulation by the Mpl ligand thrombopoietin, also had reduced expression of the activated transcription factors p-STAT3 and p-STAT5, compared with controls.

Finally, the researchers examined human CML cells for differences between MPL-Hi LTHSCs and MPL-Lo LTHSCs. The results were similar to those observed in mice.

The human MPL-Hi LTHSCs had a higher rate of engraftment than the human MPL-Lo LTHSCs, as tested in a xenograft model using immunodeficient mice.

Additionally, the human MPL-Hi LTHSCs had reduced sensitivity to nilotinib compared with MPL-Lo LTHSCs. However, a Jak/STAT inhibitor significantly reduced cell growth and increased apoptosis in human MPL-Hi LTHSCs.

The researchers concluded that MPL expression is a marker and key regulator of leukemogenic potential and drug sensitivity of CML LTHSCs. They said their findings support further investigation of approaches to antagonize MPL signaling as a potential therapeutic strategy to eliminate leukemia-initiating LTHSCs.

Researcher in the lab

Photo by Daniel Sone

A study published in The BMJ indicates that leading US academic medical centers often fail to report clinical trial results in a timely manner, despite ethical obligations and even statutory requirements to do so.

Of the more than 4000 clinical trials studied, 67% had results disseminated at some point after trial completion, 29% were published within 2 years of completion, and 13% had results posted on ClinicalTrials.gov within 2 years of completion.

Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, and his colleagues conducted this study.

They evaluated 4347 registered trials conducted at 51 leading US academic institutions and completed between October 2007 and September 2010.

Overall, 67% of the trials (2892/4347) had been published or had results reported as of July 2014. Thirty-six percent (n=1560) had results disseminated within 2 years of trial completion.

Fifty-seven percent of trials (n=2458) had been published as of July 2014, and 29% (n=1245) were published within 2 years of completion.

Twenty-seven percent of trials (n=1166) had results reported on ClinicalTrials.gov as of July 2014, and 13% (n=547) had results reported within 2 years of completion.

There was marked variation in the dissemination of trial results across institutions. There was a more than 2-fold variation in the average time from study completion to dissemination of results and a more than 3-fold variation in the rate of dissemination across institutions.

Dr Krumholz and his colleagues noted that there are no repercussions to academic institutions or individual investigators for failing to report trial results, and there is no effective enforcement mechanism.

Researcher in the lab

Photo by Daniel Sone

A study published in The BMJ indicates that leading US academic medical centers often fail to report clinical trial results in a timely manner, despite ethical obligations and even statutory requirements to do so.

Of the more than 4000 clinical trials studied, 67% had results disseminated at some point after trial completion, 29% were published within 2 years of completion, and 13% had results posted on ClinicalTrials.gov within 2 years of completion.

Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, and his colleagues conducted this study.

They evaluated 4347 registered trials conducted at 51 leading US academic institutions and completed between October 2007 and September 2010.

Overall, 67% of the trials (2892/4347) had been published or had results reported as of July 2014. Thirty-six percent (n=1560) had results disseminated within 2 years of trial completion.

Fifty-seven percent of trials (n=2458) had been published as of July 2014, and 29% (n=1245) were published within 2 years of completion.

Twenty-seven percent of trials (n=1166) had results reported on ClinicalTrials.gov as of July 2014, and 13% (n=547) had results reported within 2 years of completion.

There was marked variation in the dissemination of trial results across institutions. There was a more than 2-fold variation in the average time from study completion to dissemination of results and a more than 3-fold variation in the rate of dissemination across institutions.

Dr Krumholz and his colleagues noted that there are no repercussions to academic institutions or individual investigators for failing to report trial results, and there is no effective enforcement mechanism.

Researcher in the lab

Photo by Daniel Sone

A study published in The BMJ indicates that leading US academic medical centers often fail to report clinical trial results in a timely manner, despite ethical obligations and even statutory requirements to do so.

Of the more than 4000 clinical trials studied, 67% had results disseminated at some point after trial completion, 29% were published within 2 years of completion, and 13% had results posted on ClinicalTrials.gov within 2 years of completion.

Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, and his colleagues conducted this study.

They evaluated 4347 registered trials conducted at 51 leading US academic institutions and completed between October 2007 and September 2010.

Overall, 67% of the trials (2892/4347) had been published or had results reported as of July 2014. Thirty-six percent (n=1560) had results disseminated within 2 years of trial completion.

Fifty-seven percent of trials (n=2458) had been published as of July 2014, and 29% (n=1245) were published within 2 years of completion.

Twenty-seven percent of trials (n=1166) had results reported on ClinicalTrials.gov as of July 2014, and 13% (n=547) had results reported within 2 years of completion.

There was marked variation in the dissemination of trial results across institutions. There was a more than 2-fold variation in the average time from study completion to dissemination of results and a more than 3-fold variation in the rate of dissemination across institutions.

Dr Krumholz and his colleagues noted that there are no repercussions to academic institutions or individual investigators for failing to report trial results, and there is no effective enforcement mechanism.

Blood for transfusion

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has issued a new guidance recommending the deferral of blood donors who have been to areas with active Zika virus transmission, may have been exposed to the virus, or have had a confirmed Zika virus infection.

In areas of the US without active Zika virus transmission, the FDA recommends that donors at risk for Zika virus infection be deferred for 4 weeks.

Individuals considered to be at risk include those who have had symptoms suggestive of Zika virus infection during the past 4 weeks, those who have had sexual contact with a person who has traveled to or resided in an area with active Zika virus transmission during the prior 3 months, and those who have traveled to areas with active transmission of Zika virus during the past 4 weeks.

In areas of the US with active Zika virus transmission (at present, the Commonwealth of Puerto Rico, the US Virgin Islands, and American Samoa), the FDA recommends that whole blood and blood components for transfusion be obtained from areas of the US without active transmission.

Blood establishments may continue collecting and preparing platelets and plasma if an FDA-approved pathogen-reduction device is used.

The FDA’s guidance also recommends that blood establishments update donor education materials with information about the signs and symptoms of Zika virus and ask potentially affected donors to refrain from giving blood.

“Based on the best available evidence, we believe the new recommendations will help reduce the risk of collecting blood and blood components from donors who may be infected with the Zika virus,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

There have been no reports to date of Zika virus entering the US blood supply. However, the risk of blood transmission is considered likely based on the most current scientific evidence of how Zika virus and similar viruses (flaviviruses) are spread and recent reports of transfusion-associated infection outside the US.

Furthermore, about 4 out of 5 people infected with Zika virus do not become symptomatic. For these reasons, the FDA is recommending that blood establishments defer blood donations in accordance with the new guidance.

The FDA also intends to issue a guidance that will address appropriate donor deferral measures for human cells, tissues, and cellular and tissue-based products, given recent reports of sexual transmission of the Zika virus.

In addition, the FDA is prioritizing the development of blood screening and diagnostic tests that may be useful for identifying the Zika virus, preparing to evaluate the safety and efficacy of investigational vaccines and therapeutics that might be developed, and reviewing technology that may help suppress populations of mosquitoes that can spread the virus.

Blood for transfusion

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has issued a new guidance recommending the deferral of blood donors who have been to areas with active Zika virus transmission, may have been exposed to the virus, or have had a confirmed Zika virus infection.

In areas of the US without active Zika virus transmission, the FDA recommends that donors at risk for Zika virus infection be deferred for 4 weeks.

Individuals considered to be at risk include those who have had symptoms suggestive of Zika virus infection during the past 4 weeks, those who have had sexual contact with a person who has traveled to or resided in an area with active Zika virus transmission during the prior 3 months, and those who have traveled to areas with active transmission of Zika virus during the past 4 weeks.

In areas of the US with active Zika virus transmission (at present, the Commonwealth of Puerto Rico, the US Virgin Islands, and American Samoa), the FDA recommends that whole blood and blood components for transfusion be obtained from areas of the US without active transmission.

Blood establishments may continue collecting and preparing platelets and plasma if an FDA-approved pathogen-reduction device is used.

The FDA’s guidance also recommends that blood establishments update donor education materials with information about the signs and symptoms of Zika virus and ask potentially affected donors to refrain from giving blood.

“Based on the best available evidence, we believe the new recommendations will help reduce the risk of collecting blood and blood components from donors who may be infected with the Zika virus,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

There have been no reports to date of Zika virus entering the US blood supply. However, the risk of blood transmission is considered likely based on the most current scientific evidence of how Zika virus and similar viruses (flaviviruses) are spread and recent reports of transfusion-associated infection outside the US.

Furthermore, about 4 out of 5 people infected with Zika virus do not become symptomatic. For these reasons, the FDA is recommending that blood establishments defer blood donations in accordance with the new guidance.

The FDA also intends to issue a guidance that will address appropriate donor deferral measures for human cells, tissues, and cellular and tissue-based products, given recent reports of sexual transmission of the Zika virus.

In addition, the FDA is prioritizing the development of blood screening and diagnostic tests that may be useful for identifying the Zika virus, preparing to evaluate the safety and efficacy of investigational vaccines and therapeutics that might be developed, and reviewing technology that may help suppress populations of mosquitoes that can spread the virus.

Blood for transfusion

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has issued a new guidance recommending the deferral of blood donors who have been to areas with active Zika virus transmission, may have been exposed to the virus, or have had a confirmed Zika virus infection.

In areas of the US without active Zika virus transmission, the FDA recommends that donors at risk for Zika virus infection be deferred for 4 weeks.

Individuals considered to be at risk include those who have had symptoms suggestive of Zika virus infection during the past 4 weeks, those who have had sexual contact with a person who has traveled to or resided in an area with active Zika virus transmission during the prior 3 months, and those who have traveled to areas with active transmission of Zika virus during the past 4 weeks.

In areas of the US with active Zika virus transmission (at present, the Commonwealth of Puerto Rico, the US Virgin Islands, and American Samoa), the FDA recommends that whole blood and blood components for transfusion be obtained from areas of the US without active transmission.

Blood establishments may continue collecting and preparing platelets and plasma if an FDA-approved pathogen-reduction device is used.

The FDA’s guidance also recommends that blood establishments update donor education materials with information about the signs and symptoms of Zika virus and ask potentially affected donors to refrain from giving blood.

“Based on the best available evidence, we believe the new recommendations will help reduce the risk of collecting blood and blood components from donors who may be infected with the Zika virus,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

There have been no reports to date of Zika virus entering the US blood supply. However, the risk of blood transmission is considered likely based on the most current scientific evidence of how Zika virus and similar viruses (flaviviruses) are spread and recent reports of transfusion-associated infection outside the US.

Furthermore, about 4 out of 5 people infected with Zika virus do not become symptomatic. For these reasons, the FDA is recommending that blood establishments defer blood donations in accordance with the new guidance.

The FDA also intends to issue a guidance that will address appropriate donor deferral measures for human cells, tissues, and cellular and tissue-based products, given recent reports of sexual transmission of the Zika virus.

In addition, the FDA is prioritizing the development of blood screening and diagnostic tests that may be useful for identifying the Zika virus, preparing to evaluate the safety and efficacy of investigational vaccines and therapeutics that might be developed, and reviewing technology that may help suppress populations of mosquitoes that can spread the virus.