Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has granted orphan designation to STRO-001 for the treatment of multiple myeloma (MM).

STRO-001 is an antibody-drug conjugate targeting CD74, a protein highly expressed in MM and other B-cell malignancies.

Sutro Biopharma, Inc., is currently studying STRO-001 in a phase 1 trial enrolling separate dose-escalation cohorts for MM and B-cell lymphoma.

Preclinical research of STRO-001 in MM was presented at the 2017 ASH Annual Meeting.

Researchers examined bone marrow samples from MM patients and detected CD74 expression in 35 of the 36 samples, including specimens from patients who were treatment-naïve and patients who had been heavily pretreated with chemotherapy and stem cell transplant.

The researchers then found that STRO-001 demonstrated cytotoxicity in MM cell lines.

STRO-001 also reduced tumor burden in two disseminated xenograft models (ARP-1 and MM.1S) and prolonged survival in one of them (MM.1S).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has granted orphan designation to STRO-001 for the treatment of multiple myeloma (MM).

STRO-001 is an antibody-drug conjugate targeting CD74, a protein highly expressed in MM and other B-cell malignancies.

Sutro Biopharma, Inc., is currently studying STRO-001 in a phase 1 trial enrolling separate dose-escalation cohorts for MM and B-cell lymphoma.

Preclinical research of STRO-001 in MM was presented at the 2017 ASH Annual Meeting.

Researchers examined bone marrow samples from MM patients and detected CD74 expression in 35 of the 36 samples, including specimens from patients who were treatment-naïve and patients who had been heavily pretreated with chemotherapy and stem cell transplant.

The researchers then found that STRO-001 demonstrated cytotoxicity in MM cell lines.

STRO-001 also reduced tumor burden in two disseminated xenograft models (ARP-1 and MM.1S) and prolonged survival in one of them (MM.1S).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has granted orphan designation to STRO-001 for the treatment of multiple myeloma (MM).

STRO-001 is an antibody-drug conjugate targeting CD74, a protein highly expressed in MM and other B-cell malignancies.

Sutro Biopharma, Inc., is currently studying STRO-001 in a phase 1 trial enrolling separate dose-escalation cohorts for MM and B-cell lymphoma.

Preclinical research of STRO-001 in MM was presented at the 2017 ASH Annual Meeting.

Researchers examined bone marrow samples from MM patients and detected CD74 expression in 35 of the 36 samples, including specimens from patients who were treatment-naïve and patients who had been heavily pretreated with chemotherapy and stem cell transplant.

The researchers then found that STRO-001 demonstrated cytotoxicity in MM cell lines.

STRO-001 also reduced tumor burden in two disseminated xenograft models (ARP-1 and MM.1S) and prolonged survival in one of them (MM.1S).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5-22.9 kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colorectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5-22.9 kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colorectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5-22.9 kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colorectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

The development of a 3-D brain organoid that contains all six of the major cell types found in adult human brain cortex will be the featured topic of a presentation at the Young Research Forum of the International Conference on Parkinson’s Disease and Movement Disorders in New York on Oct. 20.

Goodwell Nzou, a doctoral student at Wake Forest University, Winston-Salem, N.C., will give the presentation, titled “The development of a multicellular three dimensional neurovascular unit model with a functional blood-brain barrier” at 1:45 p.m.

In the study that Mr. Nzou and his colleagues at the Wake Forest Institute for Regenerative Medicine published in May in Scientific Reports, they noted that, in addition to the model’s use of all six of the major cell types found in adult human brain cortex (human brain microvascular endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons), they found that it also promotes the formation of a blood-brain barrier that mimics normal human anatomy.

The researchers said their 3-D in vitro system could have potential applications in drug discovery, toxicity screening, and disease modeling for neurologic diseases such as Alzheimer’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. They demonstrated the model’s use in toxicity assessment studies for molecules that have the potential to cross or open the blood-brain barrier and also reported establishing a model of the blood-brain barrier during clinical ischemia “showing physiologic responses under hypoxic conditions.”

[email protected]

The development of a 3-D brain organoid that contains all six of the major cell types found in adult human brain cortex will be the featured topic of a presentation at the Young Research Forum of the International Conference on Parkinson’s Disease and Movement Disorders in New York on Oct. 20.

Goodwell Nzou, a doctoral student at Wake Forest University, Winston-Salem, N.C., will give the presentation, titled “The development of a multicellular three dimensional neurovascular unit model with a functional blood-brain barrier” at 1:45 p.m.

In the study that Mr. Nzou and his colleagues at the Wake Forest Institute for Regenerative Medicine published in May in Scientific Reports, they noted that, in addition to the model’s use of all six of the major cell types found in adult human brain cortex (human brain microvascular endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons), they found that it also promotes the formation of a blood-brain barrier that mimics normal human anatomy.

The researchers said their 3-D in vitro system could have potential applications in drug discovery, toxicity screening, and disease modeling for neurologic diseases such as Alzheimer’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. They demonstrated the model’s use in toxicity assessment studies for molecules that have the potential to cross or open the blood-brain barrier and also reported establishing a model of the blood-brain barrier during clinical ischemia “showing physiologic responses under hypoxic conditions.”

[email protected]

The development of a 3-D brain organoid that contains all six of the major cell types found in adult human brain cortex will be the featured topic of a presentation at the Young Research Forum of the International Conference on Parkinson’s Disease and Movement Disorders in New York on Oct. 20.

Goodwell Nzou, a doctoral student at Wake Forest University, Winston-Salem, N.C., will give the presentation, titled “The development of a multicellular three dimensional neurovascular unit model with a functional blood-brain barrier” at 1:45 p.m.

In the study that Mr. Nzou and his colleagues at the Wake Forest Institute for Regenerative Medicine published in May in Scientific Reports, they noted that, in addition to the model’s use of all six of the major cell types found in adult human brain cortex (human brain microvascular endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons), they found that it also promotes the formation of a blood-brain barrier that mimics normal human anatomy.

The researchers said their 3-D in vitro system could have potential applications in drug discovery, toxicity screening, and disease modeling for neurologic diseases such as Alzheimer’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. They demonstrated the model’s use in toxicity assessment studies for molecules that have the potential to cross or open the blood-brain barrier and also reported establishing a model of the blood-brain barrier during clinical ischemia “showing physiologic responses under hypoxic conditions.”

[email protected]

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – Higher vitamin D levels at multiple sclerosis onset were predictive of higher cognitive function 11 years on, and heavy smokers took a “clinically significant” cognitive hit, according to a recent study.

“Higher vitamin D in the first years after [clinically isolated syndrome] was associated with better cognitive function and lower neuronal injury at year 11,” said Marianna Cortese, MD, presenting her findings during a late-breaking abstracts session at the annual congress of the European Society for Education and Treatment in Multiple Sclerosis.

“Vitamin D supplementation during the early years with the disease might be neuroprotective,” she said.

According to Dr. Cortese, 40%-70% of patients with MS will experience cognitive decline across their disease course; there is no currently known specific treatment for cognitive decline.

Smoking, low levels of vitamin D [as 25(OH)D], and Epstein-Barr virus (EBV) seropositivity are known risk factors for MS, and have been associated with more active MS and progressive disease, but whether these factors predict cognitive status had not been known, said Dr. Cortese of the Harvard T.H. Chan School of Public Health.

Accordingly, she said, investigators in the BENEFIT-11 trial sought to determine whether low vitamin D levels, smoking status, and EBV seropositivity detected early after the first disease manifestation in MS would affect later cognitive function.

The study is an observational study that followed 278 participants with clinically isolated syndrome (CIS) in the original BENEFIT trial, which was a randomized, double-blind, placebo-controlled trial of interferon beta-1b for early treatment of clinically isolated syndrome. The primary goal of BENEFIT-11, said Dr. Cortese, was to assess the effects of early treatment on long-term outcomes.

“To minimize reverse causation, we used exposure status in the first 2 years after CIS to predict progression outcomes at year 11,” explained Dr. Cortese. The investigators obtained biomarkers at baseline, and at study months 6, 12, and 24. Cotinine was used as a biomarker for current or recent nicotine exposure. Serum 25(OH)D levels were used to determine vitamin D levels, and immunoglobulin G levels for EBV antigen-1 were used for EBV seropositivity.

In terms of outcome measurements, the cognitive performance measure used in the study was the Paced Auditory Serial Addition Test, a validated test of processing speed, attention, and working memory, said Dr. Cortese. This test was performed at enrollment, and at study years 1, 2, 5, and 11. At study year 11, neuroaxonal injury was measured using serum neurofilament light chain levels.

In multivariable analysis, the study design adjusted for baseline age and sex, treatment allocation at baseline, unifocal versus multifocal disease seen on baseline magnetic resonance imaging, body mass index, and whether the patient was treated with steroids during the initial CIS.

“Higher quintiles of mean vitamin D levels during the first 2 years were associated with lower odds of scoring worse on the PASAT at year 11,” said Dr. Cortese (P-trend = .028). The significant trend across the quintiles “suggests a dose-response relationship,” she said.* For vitamin D levels over the first 5 years, the P-trend was .049. Dr. Cortese explained that “scoring worse” meant scoring below the median.

Looking at the effect of early vitamin D levels another way, incremental increases of 50 nmol/L of mean 25(OH)D in study months 6-24 predicted 65% lower odds of having a PASAT score below the median at year 11 (P = .027). “Within-person increases in vitamin D during the study were also significantly associated with a better PASAT score when we used the repeated measurement in a linear mixed model,” said Dr. Cortese.

Turning to the effect of smoking on cognitive function at year 11, Dr. Cortese explained that cotinine levels obtained during the first 2 years were all used to determine smoking status. If all levels were below 10 ng/mL, the participant was designated a nonsmoker (N = 125). If any levels were above 25 ng/mL, that patient was classified as a smoker. The investigators also looked at the small number of patients (N = 9) who were very heavy smokers, with cotinine levels over 191 ng/mL.

“Smokers – compared to nonsmokers – had a significantly lower standardized PASAT score at year 11,” said Dr. Cortese (P trend = .042 in age- and sex-adjusted analysis; P-trend = .056 in full multivariable analysis). “Actually, smokers had an up to 0.6-standard deviation-lower PASAT score at year 11 when we looked at heavy smokers. ...This difference corresponds to about 5 points of the PASAT, so I would say [the score is] clinically meaningful.”

Dr. Cortese pointed out that early smoking, again, showed a dose-response relationship with later cognitive status. “It continues to be important to encourage smoking cessation for patients.”

Epstein-Barr antibodies were not associated with cognitive function at year 11, according to the analysis (P-trend = .93).

“The findings of neuroaxonal injury at year 11 using serum neurofilament light-chain measures corroborated the main findings on cognitive function at year 11,” said Dr. Cortese.

For a 50-nmol higher vitamin D level within the first 5 years, neurofilament light chain levels at year 11 were 20% lower, said Dr. Cortese. Conversely, patients who had cotinine levels higher than 25 ng/mL during the first 5 years had neurofilament light chain levels 20% higher than other participants: “So they did worse. They had more neuroaxonal loss,” said Dr. Cortese. No association was seen between neurofilament light chain levels at year 11 and early EBV status, she said.

Though just cognitive function data from BENEFIT-11 were reported by Dr. Cortese, she said that radiologic and other clinical data are also being studied and will be reported in the future.

Dr. Cortese reported that she had no conflicts of interest. Several coauthors reported financial relationships with multiple pharmaceutical companies. The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society, with clinical support from Bayer HealthCare.

[email protected]

SOURCE: Cortese M et al. ECTRIMS 2018, Late breaking abstracts session.

*Correction, 10/25/18: An earlier version of this article mischaracterized the relationship between vitamin D scores during the first 2 years and PASAT scores at year 11. 

BERLIN – The monoclonal antibody satralizumab reduced by 62% relapses of neuromyelitis optica spectrum disorder (NMOSD) over 24 weeks, as compared with placebo.

Michelle Sullivan/Mdedge News

Chugai Pharmaceuticals sponsored the study. Dr. Yamamura has served as a consultant for the company and reported financial ties with numerous other drug manufacturers.

[email protected]

SOURCE: Yamamura T et al. ECTRIMS 2018, Oral abstract 323

BERLIN – The monoclonal antibody satralizumab reduced by 62% relapses of neuromyelitis optica spectrum disorder (NMOSD) over 24 weeks, as compared with placebo.

Michelle Sullivan/Mdedge News

Chugai Pharmaceuticals sponsored the study. Dr. Yamamura has served as a consultant for the company and reported financial ties with numerous other drug manufacturers.

[email protected]

SOURCE: Yamamura T et al. ECTRIMS 2018, Oral abstract 323

BERLIN – The monoclonal antibody satralizumab reduced by 62% relapses of neuromyelitis optica spectrum disorder (NMOSD) over 24 weeks, as compared with placebo.

Michelle Sullivan/Mdedge News

Chugai Pharmaceuticals sponsored the study. Dr. Yamamura has served as a consultant for the company and reported financial ties with numerous other drug manufacturers.

[email protected]

SOURCE: Yamamura T et al. ECTRIMS 2018, Oral abstract 323

Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.

Janice Haney Carr/CDC

Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.

The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.

Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.

Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.

In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.

“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).

The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.

“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.

SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.

Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.

Janice Haney Carr/CDC

Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.

The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.

Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.

Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.

In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.

“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).

The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.

“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.

SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.

Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.

Janice Haney Carr/CDC

Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.

The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.

Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.

Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.

In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.

“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).

The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.

“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.

SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.

BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.

Sara Freeman/MDedge News

SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.

BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.

Sara Freeman/MDedge News

SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.

BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.

Sara Freeman/MDedge News

SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.

Photo by Graham Colm

The U.S. Food and Drug Administration (FDA) has approved ID CORE XT, a molecular-based assay used to determine blood donor and recipient compatibility.

ID CORE XT is a qualitative, polymerase chain reaction-based and hybridization-based genotyping test.

It is used for the simultaneous identification of multiple alleles encoding human erythrocyte antigens in genomic DNA extracted from whole blood specimens collected in ethylenediaminetetraacetic acid.

The test genotypes 29 polymorphisms determining 37 human erythrocyte antigen phenotypes of 10 blood group systems—Rh, Kell, Kidd, Duffy, MNS, Diego, Dombrock, Colton, Cartwright, and Lutheran.

ID CORE XT is the second molecular assay approved by the FDA for use in transfusion medicine and the first to report genotypes as final results.

The approval of ID CORE XT was granted to Progenika Biopharma S.A., a Grifols company.

According to Progenika, ID CORE XT will benefit patients who require ongoing transfusions, such as individuals with hemoglobinopathies.

ID CORE XT can also be used for cancer patients who require more thorough blood typing, patients with warm autoimmune hemolytic anemia, and patients taking daratumumab.

“The approval of the ID CORE XT test can streamline blood compatibility testing and provides an additional alternative to testing blood with antisera,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

In a study published in Blood Transfusion this year, typing results with ID CORE XT were similar to results obtained with serology and molecular methods.

Researchers said there was 100% agreement between the positive results predicted by ID CORE XT and results obtained via serology (100% sensitivity).

For negative results, there was one discrepancy for E antigen (99.9% agreement) and 33 discrepancies for Fy^b antigen (95.5% agreement). However, additional testing suggested that serology produced 34 false-negatives.

Both positive and negative results with ID CORE XT were in full agreement with results obtained via molecular methods (100% sensitivity and specificity).

Photo by Graham Colm

The U.S. Food and Drug Administration (FDA) has approved ID CORE XT, a molecular-based assay used to determine blood donor and recipient compatibility.

ID CORE XT is a qualitative, polymerase chain reaction-based and hybridization-based genotyping test.

It is used for the simultaneous identification of multiple alleles encoding human erythrocyte antigens in genomic DNA extracted from whole blood specimens collected in ethylenediaminetetraacetic acid.

The test genotypes 29 polymorphisms determining 37 human erythrocyte antigen phenotypes of 10 blood group systems—Rh, Kell, Kidd, Duffy, MNS, Diego, Dombrock, Colton, Cartwright, and Lutheran.

ID CORE XT is the second molecular assay approved by the FDA for use in transfusion medicine and the first to report genotypes as final results.

The approval of ID CORE XT was granted to Progenika Biopharma S.A., a Grifols company.

According to Progenika, ID CORE XT will benefit patients who require ongoing transfusions, such as individuals with hemoglobinopathies.

ID CORE XT can also be used for cancer patients who require more thorough blood typing, patients with warm autoimmune hemolytic anemia, and patients taking daratumumab.

“The approval of the ID CORE XT test can streamline blood compatibility testing and provides an additional alternative to testing blood with antisera,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

In a study published in Blood Transfusion this year, typing results with ID CORE XT were similar to results obtained with serology and molecular methods.

Researchers said there was 100% agreement between the positive results predicted by ID CORE XT and results obtained via serology (100% sensitivity).

For negative results, there was one discrepancy for E antigen (99.9% agreement) and 33 discrepancies for Fy^b antigen (95.5% agreement). However, additional testing suggested that serology produced 34 false-negatives.

Both positive and negative results with ID CORE XT were in full agreement with results obtained via molecular methods (100% sensitivity and specificity).

Photo by Graham Colm

The U.S. Food and Drug Administration (FDA) has approved ID CORE XT, a molecular-based assay used to determine blood donor and recipient compatibility.

ID CORE XT is a qualitative, polymerase chain reaction-based and hybridization-based genotyping test.

It is used for the simultaneous identification of multiple alleles encoding human erythrocyte antigens in genomic DNA extracted from whole blood specimens collected in ethylenediaminetetraacetic acid.

The test genotypes 29 polymorphisms determining 37 human erythrocyte antigen phenotypes of 10 blood group systems—Rh, Kell, Kidd, Duffy, MNS, Diego, Dombrock, Colton, Cartwright, and Lutheran.

ID CORE XT is the second molecular assay approved by the FDA for use in transfusion medicine and the first to report genotypes as final results.

The approval of ID CORE XT was granted to Progenika Biopharma S.A., a Grifols company.

According to Progenika, ID CORE XT will benefit patients who require ongoing transfusions, such as individuals with hemoglobinopathies.

ID CORE XT can also be used for cancer patients who require more thorough blood typing, patients with warm autoimmune hemolytic anemia, and patients taking daratumumab.

“The approval of the ID CORE XT test can streamline blood compatibility testing and provides an additional alternative to testing blood with antisera,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

In a study published in Blood Transfusion this year, typing results with ID CORE XT were similar to results obtained with serology and molecular methods.

Researchers said there was 100% agreement between the positive results predicted by ID CORE XT and results obtained via serology (100% sensitivity).

For negative results, there was one discrepancy for E antigen (99.9% agreement) and 33 discrepancies for Fy^b antigen (95.5% agreement). However, additional testing suggested that serology produced 34 false-negatives.

Both positive and negative results with ID CORE XT were in full agreement with results obtained via molecular methods (100% sensitivity and specificity).

ABSTRACT

Improvements in ultrasound technology have increased the popularity and use of ultrasound as a diagnostic and therapeutic modality for many soccer-related musculoskeletal (MSK) injuries. As a dynamic imaging modality, ultrasound offers increased accuracy and efficacy with minimally invasive procedures, such as guided injections, percutaneous tenotomy, and regenerative therapies, in the clinical setting. Emerging evidence indicates that regenerative therapies, such as platelet-rich-plasma (PRP), mesenchymal stem cells, and amniotic products, are a promising treatment for many MSK injuries and are gaining popularity among professional athletes. PRP is a safe treatment for a number of MSK conditions and has been included in the standard of care. However, conflicting evidence on return-to-play timeframes and efficacy in certain MSK conditions have led to inconsistent recommendations on indications for use, dose, and timing of treatment. Mesenchymal stem cell therapy, while promising, lacks high-level evidence of efficacy despite its increasing use among athletes. Currently, no data are available regarding the outcome of the use of amniotic products for the treatment of injuries in athletes. Furthermore, preparation of many regenerative therapies eclipses the concept of minimal manipulation and is subject to US Food and Drug Administration phase I to III trials. High-level research on regenerative medicine therapies should be continuously conducted to establish their clinical efficacy and safety data.

ABSTRACT

Improvements in ultrasound technology have increased the popularity and use of ultrasound as a diagnostic and therapeutic modality for many soccer-related musculoskeletal (MSK) injuries. As a dynamic imaging modality, ultrasound offers increased accuracy and efficacy with minimally invasive procedures, such as guided injections, percutaneous tenotomy, and regenerative therapies, in the clinical setting. Emerging evidence indicates that regenerative therapies, such as platelet-rich-plasma (PRP), mesenchymal stem cells, and amniotic products, are a promising treatment for many MSK injuries and are gaining popularity among professional athletes. PRP is a safe treatment for a number of MSK conditions and has been included in the standard of care. However, conflicting evidence on return-to-play timeframes and efficacy in certain MSK conditions have led to inconsistent recommendations on indications for use, dose, and timing of treatment. Mesenchymal stem cell therapy, while promising, lacks high-level evidence of efficacy despite its increasing use among athletes. Currently, no data are available regarding the outcome of the use of amniotic products for the treatment of injuries in athletes. Furthermore, preparation of many regenerative therapies eclipses the concept of minimal manipulation and is subject to US Food and Drug Administration phase I to III trials. High-level research on regenerative medicine therapies should be continuously conducted to establish their clinical efficacy and safety data.

ABSTRACT

Improvements in ultrasound technology have increased the popularity and use of ultrasound as a diagnostic and therapeutic modality for many soccer-related musculoskeletal (MSK) injuries. As a dynamic imaging modality, ultrasound offers increased accuracy and efficacy with minimally invasive procedures, such as guided injections, percutaneous tenotomy, and regenerative therapies, in the clinical setting. Emerging evidence indicates that regenerative therapies, such as platelet-rich-plasma (PRP), mesenchymal stem cells, and amniotic products, are a promising treatment for many MSK injuries and are gaining popularity among professional athletes. PRP is a safe treatment for a number of MSK conditions and has been included in the standard of care. However, conflicting evidence on return-to-play timeframes and efficacy in certain MSK conditions have led to inconsistent recommendations on indications for use, dose, and timing of treatment. Mesenchymal stem cell therapy, while promising, lacks high-level evidence of efficacy despite its increasing use among athletes. Currently, no data are available regarding the outcome of the use of amniotic products for the treatment of injuries in athletes. Furthermore, preparation of many regenerative therapies eclipses the concept of minimal manipulation and is subject to US Food and Drug Administration phase I to III trials. High-level research on regenerative medicine therapies should be continuously conducted to establish their clinical efficacy and safety data.