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.”

jevans@mdedge.com

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.”

jevans@mdedge.com

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.”

jevans@mdedge.com

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.

koakes@mdedge.com

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.

koakes@mdedge.com

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.

koakes@mdedge.com

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.

msullivan@mdedge.com

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.

msullivan@mdedge.com

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.

msullivan@mdedge.com

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.

Nearly every parent gets excited about their child’s first smile, steps, and words. Developmental and behavioral screening helps to better track young children’s progress in areas like communication, motor, cognitive, and social/emotional skills. Approximately one in four or five children are at risk for a developmental/behavioral delay, which might indicate an emerging developmental disability or mental health disorder.

Regular screenings raise awareness of children’s development, which makes it easier for parents to expect and celebrate milestones. They encourage parents and doctors to avoid the common pitfall of taking a “wait and see” approach. Regular screenings might even help doctors more easily diagnose co-occurring conditions like autism, sleep disorders, iron deficiencies, hearing impairment, metabolic disorders, genetic disorders, in utero drug/alcohol exposure, or child maltreatment.

High-quality interventions for children aged 0-5 years can decrease rates of special education, substance abuse, criminality/incarceration, suicidal attempts, and unemployment or welfare dependency. The trick is to swiftly identify and refer at-risk and delayed children to the most effective resources in a family-centered manner.

Our new study, which has been published online in Developmental Medicine and Child Neurology, investigated early childhood screening practices across the United States and Scandinavia (Denmark, Norway, and Sweden), which lie relatively far apart on the spectrum of preventive care models (2018 Sep 23. doi: 10.1111/dmcn.14044).

Just like many other developed areas of the world, the United States and Scandinavia are increasingly using two accurate, parent-reported screening tools – the Ages & Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) – to measure developmental and behavioral skills in children aged 0-5 years. We found that routine and periodic ASQ and/or ASQ:SE screening is low cost, feasible, and increases early detection and referral rates, plus they connect at-risk children to early intervention programs at significantly younger ages.

Surprisingly, the United States and Scandinavia tend to use these same two screening questionnaires quite differently. U.S. pediatricians and family physicians commonly use the ASQ and/or ASQ:SE in clinic settings to swiftly identify developmental/behavioral red flags in children from general and at-risk populations (See video at end of article). Scandinavian studies more commonly report the use of the ASQ and ASQ:SE to track developmental/behavioral differences in children in an intervention/exposure group and how they compare with children in a control group over time. In other words, the United States uses these screens clinically, and Scandinavia mostly uses them for research purposes.

In Scandinavia, home visit nurses and general practitioners commonly administer more narrowly focused, “hands-on” screens during infancy. Different municipalities use different screens. Language-focused screening typically is not performed until ages 2.5-3 years in preschools or child health centers. That’s probably too late. Scandinavian countries, which boast bountiful and equitable early childhood resources, are not routinely using parent-centered screening tools that measure all of a child’s developmental domains, including social/emotional skills. One reason is probably that Danish and Swedish ASQ and ASQ:SE norming (standardization) and validation (reliability and accuracy) studies are lacking and because Norwegian norms are out-of-date. Therefore, they are primarily used just for research. Every decade, the “good” screening questionnaires have to be scientifically tweaked and improved as the characteristics of populations (like ethnicity, socioeconomic status, or percentage of new immigrants) and cultural norms (like rotary versus cell phones) change over time.

Here is a video Dr. Marks has developed showing how to integrate ASQ screening into your practice.

Dr. Marks is a pediatrician, clinical researcher, and coauthor of Developmental Screening in Your Community. Dr. Madsen Sjö is a certified pediatric neuropsychologist in Copenhagen. Dr. Marks and his family moved from the United States to Denmark in 2017. Email him at pdnews@mdedge.com.

Nearly every parent gets excited about their child’s first smile, steps, and words. Developmental and behavioral screening helps to better track young children’s progress in areas like communication, motor, cognitive, and social/emotional skills. Approximately one in four or five children are at risk for a developmental/behavioral delay, which might indicate an emerging developmental disability or mental health disorder.

Regular screenings raise awareness of children’s development, which makes it easier for parents to expect and celebrate milestones. They encourage parents and doctors to avoid the common pitfall of taking a “wait and see” approach. Regular screenings might even help doctors more easily diagnose co-occurring conditions like autism, sleep disorders, iron deficiencies, hearing impairment, metabolic disorders, genetic disorders, in utero drug/alcohol exposure, or child maltreatment.

High-quality interventions for children aged 0-5 years can decrease rates of special education, substance abuse, criminality/incarceration, suicidal attempts, and unemployment or welfare dependency. The trick is to swiftly identify and refer at-risk and delayed children to the most effective resources in a family-centered manner.

Our new study, which has been published online in Developmental Medicine and Child Neurology, investigated early childhood screening practices across the United States and Scandinavia (Denmark, Norway, and Sweden), which lie relatively far apart on the spectrum of preventive care models (2018 Sep 23. doi: 10.1111/dmcn.14044).

Just like many other developed areas of the world, the United States and Scandinavia are increasingly using two accurate, parent-reported screening tools – the Ages & Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) – to measure developmental and behavioral skills in children aged 0-5 years. We found that routine and periodic ASQ and/or ASQ:SE screening is low cost, feasible, and increases early detection and referral rates, plus they connect at-risk children to early intervention programs at significantly younger ages.

Surprisingly, the United States and Scandinavia tend to use these same two screening questionnaires quite differently. U.S. pediatricians and family physicians commonly use the ASQ and/or ASQ:SE in clinic settings to swiftly identify developmental/behavioral red flags in children from general and at-risk populations (See video at end of article). Scandinavian studies more commonly report the use of the ASQ and ASQ:SE to track developmental/behavioral differences in children in an intervention/exposure group and how they compare with children in a control group over time. In other words, the United States uses these screens clinically, and Scandinavia mostly uses them for research purposes.

In Scandinavia, home visit nurses and general practitioners commonly administer more narrowly focused, “hands-on” screens during infancy. Different municipalities use different screens. Language-focused screening typically is not performed until ages 2.5-3 years in preschools or child health centers. That’s probably too late. Scandinavian countries, which boast bountiful and equitable early childhood resources, are not routinely using parent-centered screening tools that measure all of a child’s developmental domains, including social/emotional skills. One reason is probably that Danish and Swedish ASQ and ASQ:SE norming (standardization) and validation (reliability and accuracy) studies are lacking and because Norwegian norms are out-of-date. Therefore, they are primarily used just for research. Every decade, the “good” screening questionnaires have to be scientifically tweaked and improved as the characteristics of populations (like ethnicity, socioeconomic status, or percentage of new immigrants) and cultural norms (like rotary versus cell phones) change over time.

Here is a video Dr. Marks has developed showing how to integrate ASQ screening into your practice.

Dr. Marks is a pediatrician, clinical researcher, and coauthor of Developmental Screening in Your Community. Dr. Madsen Sjö is a certified pediatric neuropsychologist in Copenhagen. Dr. Marks and his family moved from the United States to Denmark in 2017. Email him at pdnews@mdedge.com.

Nearly every parent gets excited about their child’s first smile, steps, and words. Developmental and behavioral screening helps to better track young children’s progress in areas like communication, motor, cognitive, and social/emotional skills. Approximately one in four or five children are at risk for a developmental/behavioral delay, which might indicate an emerging developmental disability or mental health disorder.

Regular screenings raise awareness of children’s development, which makes it easier for parents to expect and celebrate milestones. They encourage parents and doctors to avoid the common pitfall of taking a “wait and see” approach. Regular screenings might even help doctors more easily diagnose co-occurring conditions like autism, sleep disorders, iron deficiencies, hearing impairment, metabolic disorders, genetic disorders, in utero drug/alcohol exposure, or child maltreatment.

High-quality interventions for children aged 0-5 years can decrease rates of special education, substance abuse, criminality/incarceration, suicidal attempts, and unemployment or welfare dependency. The trick is to swiftly identify and refer at-risk and delayed children to the most effective resources in a family-centered manner.

Our new study, which has been published online in Developmental Medicine and Child Neurology, investigated early childhood screening practices across the United States and Scandinavia (Denmark, Norway, and Sweden), which lie relatively far apart on the spectrum of preventive care models (2018 Sep 23. doi: 10.1111/dmcn.14044).

Just like many other developed areas of the world, the United States and Scandinavia are increasingly using two accurate, parent-reported screening tools – the Ages & Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) – to measure developmental and behavioral skills in children aged 0-5 years. We found that routine and periodic ASQ and/or ASQ:SE screening is low cost, feasible, and increases early detection and referral rates, plus they connect at-risk children to early intervention programs at significantly younger ages.

Surprisingly, the United States and Scandinavia tend to use these same two screening questionnaires quite differently. U.S. pediatricians and family physicians commonly use the ASQ and/or ASQ:SE in clinic settings to swiftly identify developmental/behavioral red flags in children from general and at-risk populations (See video at end of article). Scandinavian studies more commonly report the use of the ASQ and ASQ:SE to track developmental/behavioral differences in children in an intervention/exposure group and how they compare with children in a control group over time. In other words, the United States uses these screens clinically, and Scandinavia mostly uses them for research purposes.

In Scandinavia, home visit nurses and general practitioners commonly administer more narrowly focused, “hands-on” screens during infancy. Different municipalities use different screens. Language-focused screening typically is not performed until ages 2.5-3 years in preschools or child health centers. That’s probably too late. Scandinavian countries, which boast bountiful and equitable early childhood resources, are not routinely using parent-centered screening tools that measure all of a child’s developmental domains, including social/emotional skills. One reason is probably that Danish and Swedish ASQ and ASQ:SE norming (standardization) and validation (reliability and accuracy) studies are lacking and because Norwegian norms are out-of-date. Therefore, they are primarily used just for research. Every decade, the “good” screening questionnaires have to be scientifically tweaked and improved as the characteristics of populations (like ethnicity, socioeconomic status, or percentage of new immigrants) and cultural norms (like rotary versus cell phones) change over time.

Here is a video Dr. Marks has developed showing how to integrate ASQ screening into your practice.

Dr. Marks is a pediatrician, clinical researcher, and coauthor of Developmental Screening in Your Community. Dr. Madsen Sjö is a certified pediatric neuropsychologist in Copenhagen. Dr. Marks and his family moved from the United States to Denmark in 2017. Email him at pdnews@mdedge.com.

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

bjancin@mdedge.com

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

bjancin@mdedge.com

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

bjancin@mdedge.com

A 57-year-old man is admitted to the hospital with new back pain, which has been getting worse over the past 6 days. He had been diagnosed with stage 4 lung cancer in mid-2017 and underwent treatment with a platinum-based double therapy.

The man also has a history of heroin use – as recently as two years earlier – and he was divorced not long ago. He has been using an old prescription for Vicodin to treat himself, taking as many as 10-12 tablets a day.

This man is an example of the kind of complicated patient hospitalists are called on to treat – complex pain in an era when opioid abuse is considered a public scourge. How is a hospitalist to handle a case like this?

Pain cases are far from the only types of increasingly complex, often palliative cases in which hospitalists are being asked to provide help. Care for the elderly is also becoming increasingly difficult as the U.S. population ages and as hospitalists step in to provide care in the absence of geriatricians. .

Pain management in the opioid era and the need for new approaches in elderly care were highlighted at the Hospital Medicine 2018 annual conference, with experts drawing attention to subtleties that are often overlooked in these sometimes desperate cases.

James Risser, MD, medical director of palliative care at Regions Hospital in Minneapolis, said the complex problems of the 57-year-old man with back pain amounted to an example of “pain’s greatest hits.”

That particular case underscores the need to identify individual types of pain, he said, because they all need to be handled differently. If hospitalists don’t consider all the different aspects of pain, a patient might endure more suffering than necessary.

“All of this pain is swirling around in a very complicated patient,” Dr. Risser said, noting that it is important to “tease out the individual parts” of a complex patient’s history.

“Pain is a very complicated construct, from the physical to the neurological to the emotional,” Dr. Risser said. “Pain is a subjective experience, and the way people interact with their pain really depends not just on physical pain but also their psychological state, their social state, and even their spiritual state.”

Understanding this array of causes has led Dr. Risser to approach the problem of pain from different angles – including perspectives that might not be traditional, he said.

“One of the things that I’ve gotten better at is taking a spiritual history,” he said. “I don’t know if that’s part of everybody’s armamentarium. But if you’re dealing with people who are very, very sick, sometimes that’s the fundamental fabric of how they live and how they die. If there are unresolved issues along those lines, it’s possible they could be experiencing their pain in a different or more severe way.”
 

Varieties of pain

Treatment depends on the pain type, Dr. Risser said. Somatic pain often responds to nonsteroidal anti-inflammatories or steroids.

ah_designs/Getty Images

Neuropathic pain usually responds poorly to anti-inflammatories and to opioids. There is some research suggesting methadone could be helpful, but the data are not very strong. The most common medications prescribed are antiseizure medications and antidepressants, such as gabapentin and serotonin, and norepinephrine reuptake inhibitors.

The question of cancer pain versus noncancer pain can be tricky, Dr. Risser said. If a person’s life expectancy is limited, there can be a reason, or even a requirement, to use higher-risk medications. But, he said, that doesn’t mean the patient still won’t have problems with overuse of pain medication.

“We have a lot of patients now living post cancer who have been put on methadone or have been put on Oxycontin, and now we’re trying to figure out what to do with them,” he said. “I don’t think it’s that clear anymore that there’s a massive difference between cancer and noncancer pain, especially for those survivors.”

Clinicians, he said, should “fix what can be fixed” – and with the right tools. “If you have a patient who’s got severe lower abdominal pain because they have a bladder full or urine, really the treatment would probably not be … opioids. It probably would be a Foley catheter,” he said.

Hospitalists should treat patients based on sound principles of pain management, Dr. Risser said, but “while you try to create a diagnostic framework, know that people continually defy the boxes we put them in.”

Indeed, in an era of pain-medication addiction, it might be a good idea to worry about prescribing opioids, but clinicians have to remember that their goal is to help patients get relief – and that they themselves bring biases to the table, said Amy Davis, DO, MS, of Drexel University, Philadelphia.

In a presentation at HM18, Dr. Davis displayed images of a variety of patients on a large screen – different races and genders, some in business attire, some rougher around the edges.

“Would pain decisions change based on what people look like?” she asked. “Can you really spot who the drug traffickers are? We need to remember that our biases play a huge role not only in the treatment of our patients but in their outcomes. I’m challenging everybody to start thinking about these folks not as drug-seekers but as comfort-seekers.”

When it comes right down to it, she said, patients want a better life, not their drug of choice.

“That is the nature of the disease. [The illegal drug] is not what they’re looking for in reality because that does not provide a good quality of life,” Dr. Davis said. “The [practice of medicine] is supposed to be about helping people live their lives, not just checking off boxes.”

People with an opioid use disorder are physically different, she said. The processing of pain stimuli by their brain and spinal cord is physically altered – they have an increased perception of pain and lower pain tolerance.

“This is not a character flaw,” Dr. Davis affirmed. The increased sensitivity to pain does not resolve with opioid cessation; it can last for decades. Clinicians may need to spend more time interacting with certain patients to get a sense of the physical and nonphysical pain from which they suffer.

“Consistent, open, nonjudgmental communication improves not only the information we gather from patients and families, but it actually changes the adherence,” Dr. Davis said. “Ultimately the treatment outcomes are what all of this is about.”
 

Paradigm shift

Another palliative care role that hospitalists often find themselves in is “comforter” of elderly patients.

Dan Burke Photography

References

1. Greysen SR et al. Functional impairment and hospital readmission in medicare seniors. JAMA Intern Med. 2015 Apr;175(4):559-65.

2. Greysen SR et al. Functional impairment: An unmeasured marker of medicare costs for postacute care of older adults. J Am Geriatr Soc. 2017 Sep;65(9):1996-2002.

3. Laura A. Levit, Erin P. Balogh, Sharyl J. Nass, and Patricia A. Ganz, eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. (Washington (DC): National Academies Press (US), 2013 Dec 27).

A 57-year-old man is admitted to the hospital with new back pain, which has been getting worse over the past 6 days. He had been diagnosed with stage 4 lung cancer in mid-2017 and underwent treatment with a platinum-based double therapy.

The man also has a history of heroin use – as recently as two years earlier – and he was divorced not long ago. He has been using an old prescription for Vicodin to treat himself, taking as many as 10-12 tablets a day.

This man is an example of the kind of complicated patient hospitalists are called on to treat – complex pain in an era when opioid abuse is considered a public scourge. How is a hospitalist to handle a case like this?

Pain cases are far from the only types of increasingly complex, often palliative cases in which hospitalists are being asked to provide help. Care for the elderly is also becoming increasingly difficult as the U.S. population ages and as hospitalists step in to provide care in the absence of geriatricians. .

Pain management in the opioid era and the need for new approaches in elderly care were highlighted at the Hospital Medicine 2018 annual conference, with experts drawing attention to subtleties that are often overlooked in these sometimes desperate cases.

James Risser, MD, medical director of palliative care at Regions Hospital in Minneapolis, said the complex problems of the 57-year-old man with back pain amounted to an example of “pain’s greatest hits.”

That particular case underscores the need to identify individual types of pain, he said, because they all need to be handled differently. If hospitalists don’t consider all the different aspects of pain, a patient might endure more suffering than necessary.

“All of this pain is swirling around in a very complicated patient,” Dr. Risser said, noting that it is important to “tease out the individual parts” of a complex patient’s history.

“Pain is a very complicated construct, from the physical to the neurological to the emotional,” Dr. Risser said. “Pain is a subjective experience, and the way people interact with their pain really depends not just on physical pain but also their psychological state, their social state, and even their spiritual state.”

Understanding this array of causes has led Dr. Risser to approach the problem of pain from different angles – including perspectives that might not be traditional, he said.

“One of the things that I’ve gotten better at is taking a spiritual history,” he said. “I don’t know if that’s part of everybody’s armamentarium. But if you’re dealing with people who are very, very sick, sometimes that’s the fundamental fabric of how they live and how they die. If there are unresolved issues along those lines, it’s possible they could be experiencing their pain in a different or more severe way.”
 

Varieties of pain

Treatment depends on the pain type, Dr. Risser said. Somatic pain often responds to nonsteroidal anti-inflammatories or steroids.

ah_designs/Getty Images

Neuropathic pain usually responds poorly to anti-inflammatories and to opioids. There is some research suggesting methadone could be helpful, but the data are not very strong. The most common medications prescribed are antiseizure medications and antidepressants, such as gabapentin and serotonin, and norepinephrine reuptake inhibitors.

The question of cancer pain versus noncancer pain can be tricky, Dr. Risser said. If a person’s life expectancy is limited, there can be a reason, or even a requirement, to use higher-risk medications. But, he said, that doesn’t mean the patient still won’t have problems with overuse of pain medication.

“We have a lot of patients now living post cancer who have been put on methadone or have been put on Oxycontin, and now we’re trying to figure out what to do with them,” he said. “I don’t think it’s that clear anymore that there’s a massive difference between cancer and noncancer pain, especially for those survivors.”

Clinicians, he said, should “fix what can be fixed” – and with the right tools. “If you have a patient who’s got severe lower abdominal pain because they have a bladder full or urine, really the treatment would probably not be … opioids. It probably would be a Foley catheter,” he said.

Hospitalists should treat patients based on sound principles of pain management, Dr. Risser said, but “while you try to create a diagnostic framework, know that people continually defy the boxes we put them in.”

Indeed, in an era of pain-medication addiction, it might be a good idea to worry about prescribing opioids, but clinicians have to remember that their goal is to help patients get relief – and that they themselves bring biases to the table, said Amy Davis, DO, MS, of Drexel University, Philadelphia.

In a presentation at HM18, Dr. Davis displayed images of a variety of patients on a large screen – different races and genders, some in business attire, some rougher around the edges.

“Would pain decisions change based on what people look like?” she asked. “Can you really spot who the drug traffickers are? We need to remember that our biases play a huge role not only in the treatment of our patients but in their outcomes. I’m challenging everybody to start thinking about these folks not as drug-seekers but as comfort-seekers.”

When it comes right down to it, she said, patients want a better life, not their drug of choice.

“That is the nature of the disease. [The illegal drug] is not what they’re looking for in reality because that does not provide a good quality of life,” Dr. Davis said. “The [practice of medicine] is supposed to be about helping people live their lives, not just checking off boxes.”

People with an opioid use disorder are physically different, she said. The processing of pain stimuli by their brain and spinal cord is physically altered – they have an increased perception of pain and lower pain tolerance.

“This is not a character flaw,” Dr. Davis affirmed. The increased sensitivity to pain does not resolve with opioid cessation; it can last for decades. Clinicians may need to spend more time interacting with certain patients to get a sense of the physical and nonphysical pain from which they suffer.

“Consistent, open, nonjudgmental communication improves not only the information we gather from patients and families, but it actually changes the adherence,” Dr. Davis said. “Ultimately the treatment outcomes are what all of this is about.”
 

Paradigm shift

Another palliative care role that hospitalists often find themselves in is “comforter” of elderly patients.

Dan Burke Photography

References

1. Greysen SR et al. Functional impairment and hospital readmission in medicare seniors. JAMA Intern Med. 2015 Apr;175(4):559-65.

2. Greysen SR et al. Functional impairment: An unmeasured marker of medicare costs for postacute care of older adults. J Am Geriatr Soc. 2017 Sep;65(9):1996-2002.

3. Laura A. Levit, Erin P. Balogh, Sharyl J. Nass, and Patricia A. Ganz, eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. (Washington (DC): National Academies Press (US), 2013 Dec 27).

A 57-year-old man is admitted to the hospital with new back pain, which has been getting worse over the past 6 days. He had been diagnosed with stage 4 lung cancer in mid-2017 and underwent treatment with a platinum-based double therapy.

The man also has a history of heroin use – as recently as two years earlier – and he was divorced not long ago. He has been using an old prescription for Vicodin to treat himself, taking as many as 10-12 tablets a day.

This man is an example of the kind of complicated patient hospitalists are called on to treat – complex pain in an era when opioid abuse is considered a public scourge. How is a hospitalist to handle a case like this?

Pain cases are far from the only types of increasingly complex, often palliative cases in which hospitalists are being asked to provide help. Care for the elderly is also becoming increasingly difficult as the U.S. population ages and as hospitalists step in to provide care in the absence of geriatricians. .

Pain management in the opioid era and the need for new approaches in elderly care were highlighted at the Hospital Medicine 2018 annual conference, with experts drawing attention to subtleties that are often overlooked in these sometimes desperate cases.

James Risser, MD, medical director of palliative care at Regions Hospital in Minneapolis, said the complex problems of the 57-year-old man with back pain amounted to an example of “pain’s greatest hits.”

That particular case underscores the need to identify individual types of pain, he said, because they all need to be handled differently. If hospitalists don’t consider all the different aspects of pain, a patient might endure more suffering than necessary.

“All of this pain is swirling around in a very complicated patient,” Dr. Risser said, noting that it is important to “tease out the individual parts” of a complex patient’s history.

“Pain is a very complicated construct, from the physical to the neurological to the emotional,” Dr. Risser said. “Pain is a subjective experience, and the way people interact with their pain really depends not just on physical pain but also their psychological state, their social state, and even their spiritual state.”

Understanding this array of causes has led Dr. Risser to approach the problem of pain from different angles – including perspectives that might not be traditional, he said.

“One of the things that I’ve gotten better at is taking a spiritual history,” he said. “I don’t know if that’s part of everybody’s armamentarium. But if you’re dealing with people who are very, very sick, sometimes that’s the fundamental fabric of how they live and how they die. If there are unresolved issues along those lines, it’s possible they could be experiencing their pain in a different or more severe way.”
 

Varieties of pain

Treatment depends on the pain type, Dr. Risser said. Somatic pain often responds to nonsteroidal anti-inflammatories or steroids.

ah_designs/Getty Images

Neuropathic pain usually responds poorly to anti-inflammatories and to opioids. There is some research suggesting methadone could be helpful, but the data are not very strong. The most common medications prescribed are antiseizure medications and antidepressants, such as gabapentin and serotonin, and norepinephrine reuptake inhibitors.

The question of cancer pain versus noncancer pain can be tricky, Dr. Risser said. If a person’s life expectancy is limited, there can be a reason, or even a requirement, to use higher-risk medications. But, he said, that doesn’t mean the patient still won’t have problems with overuse of pain medication.

“We have a lot of patients now living post cancer who have been put on methadone or have been put on Oxycontin, and now we’re trying to figure out what to do with them,” he said. “I don’t think it’s that clear anymore that there’s a massive difference between cancer and noncancer pain, especially for those survivors.”

Clinicians, he said, should “fix what can be fixed” – and with the right tools. “If you have a patient who’s got severe lower abdominal pain because they have a bladder full or urine, really the treatment would probably not be … opioids. It probably would be a Foley catheter,” he said.

Hospitalists should treat patients based on sound principles of pain management, Dr. Risser said, but “while you try to create a diagnostic framework, know that people continually defy the boxes we put them in.”

Indeed, in an era of pain-medication addiction, it might be a good idea to worry about prescribing opioids, but clinicians have to remember that their goal is to help patients get relief – and that they themselves bring biases to the table, said Amy Davis, DO, MS, of Drexel University, Philadelphia.

In a presentation at HM18, Dr. Davis displayed images of a variety of patients on a large screen – different races and genders, some in business attire, some rougher around the edges.

“Would pain decisions change based on what people look like?” she asked. “Can you really spot who the drug traffickers are? We need to remember that our biases play a huge role not only in the treatment of our patients but in their outcomes. I’m challenging everybody to start thinking about these folks not as drug-seekers but as comfort-seekers.”

When it comes right down to it, she said, patients want a better life, not their drug of choice.

“That is the nature of the disease. [The illegal drug] is not what they’re looking for in reality because that does not provide a good quality of life,” Dr. Davis said. “The [practice of medicine] is supposed to be about helping people live their lives, not just checking off boxes.”

People with an opioid use disorder are physically different, she said. The processing of pain stimuli by their brain and spinal cord is physically altered – they have an increased perception of pain and lower pain tolerance.

“This is not a character flaw,” Dr. Davis affirmed. The increased sensitivity to pain does not resolve with opioid cessation; it can last for decades. Clinicians may need to spend more time interacting with certain patients to get a sense of the physical and nonphysical pain from which they suffer.

“Consistent, open, nonjudgmental communication improves not only the information we gather from patients and families, but it actually changes the adherence,” Dr. Davis said. “Ultimately the treatment outcomes are what all of this is about.”
 

Paradigm shift

Another palliative care role that hospitalists often find themselves in is “comforter” of elderly patients.

Dan Burke Photography

References

1. Greysen SR et al. Functional impairment and hospital readmission in medicare seniors. JAMA Intern Med. 2015 Apr;175(4):559-65.

2. Greysen SR et al. Functional impairment: An unmeasured marker of medicare costs for postacute care of older adults. J Am Geriatr Soc. 2017 Sep;65(9):1996-2002.

3. Laura A. Levit, Erin P. Balogh, Sharyl J. Nass, and Patricia A. Ganz, eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. (Washington (DC): National Academies Press (US), 2013 Dec 27).