SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

More sleep can lead to better glycemic control in youth with type 1 diabetes mellitus, according to a study of sleep duration and quality in young diabetes patients.

Jovanmandic/Getty Images

“This study adds to the growing body of literature that supports the cascading effects of sleep on multiple aspects of diabetes-related outcomes,” wrote lead author Sara S. Frye, PhD, of the University of Arizona, Tucson, and her coauthors, adding that the results “highlight the importance of assessing sleep in this population that appears to be at high risk for insufficient sleep duration.” The study was published in Sleep Medicine.

Dr. Frye and her colleagues recruited 111 children between the ages of 10 and 16 with type 1 diabetes mellitus to participate in their Glucose Regulation and Neurobehavioral Effects of Sleep (GRANES) study. The participants wore wrist actigraphs for an average of 5.5 nights to objectively measure sleep, including duration, quality, timing, and consistency. They completed self-reported sleep diaries each morning of the study. Glycemic control and diabetes management were assessed via hemoglobin A_1c (HbA_1c) levels and self-monitoring of blood glucose (SMBG) frequency, which were obtained via medical records. The participants and their parents also completed the Diabetes Management Scale.

Based on actigraphy data, the average total sleep time was 7.45 hours (standard deviation, 0.74), below the recommended duration of 9 hours for youths in this age group. All but one participant was recorded as sleeping less than the recommended amount. Average HbA_1c of 9.11% (SD, 1.95) indicated poor diabetic control, and the average SMBG frequency was 4.90 (SD, 2.71) with a range of 1-14 checks per day. Per mediation analysis, for every additional hour of sleep, HbA_1c was reduced by 0.33% and SMBG frequency went up by 0.88. In addition, SMBG frequency was related to HbA_1c, supporting previous findings that “self-management behaviors play a critical role in maintaining diabetes control.”

The coauthors acknowledged the limitations of their study, including actigraphy data being logged over a 1-week period instead of the recommended 2 weeks. They also relied on medical records to determine HbA_1c and SMBG rather than collecting that information along with the actigraphy data. However, they did note that HbA1c measures glucose levels over a 3-month period, which would have covered their participation in the study.

The study was supported by American Diabetes Association and cosponsored by the Order of the Amaranth Diabetes Foundation. The authors reported no conflicts of interest.

SOURCE: Frye SS et al. Sleep Med. 2019 Feb 16. doi: 10.1016/j.sleep.2019.01.043.

The Food and Drug Administration has approved Tremfya (guselkumab) One-Press, a single-dose, patient-controlled injector, for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced.

FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).

In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.

The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.

[email protected]

The Food and Drug Administration has approved Tremfya (guselkumab) One-Press, a single-dose, patient-controlled injector, for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced.

FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).

In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.

The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.

[email protected]

The Food and Drug Administration has approved Tremfya (guselkumab) One-Press, a single-dose, patient-controlled injector, for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced.

FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).

In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.

The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.

[email protected]

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

Physicians continue to be the major drivers of hospital revenue, and the average internist generated more revenue for hospitals in 2018 than ever before, according to a new survey by physician search firm Merritt Hawkins.

“The value of physician care is not only related to the quality of patient outcomes,” Travis Singleton, the company’s executive vice president, said in a written statement. “Physicians continue to drive the financial health and viability of hospitals, even in a health care system that is evolving towards value-based payments.”

Internists generated an average of nearly $2.68 million for their affiliated hospitals last year, which was up by 46% over 2015 (the survey is conducted every 3 years) and exceeded the previous high of $2.1 million in 2003, Merritt Hawkins reported.

Primary care physicians as a group averaged just over $2.13 million in revenue in 2018, compared with almost $2.45 million for specialists, which “suggests that emerging value-based delivery models have yet to inhibit the revenue-generating power of physician specialists,” the report said. Average revenue for all physicians in all 19 specialties in the survey was almost $2.38 million, an increase of 52% since Merritt Hawkins’ last survey.

The current survey was conducted from October through December of 2018 and is based on responses from 62 chief financial officers or other financial managers who represented 93 hospitals. Responses from smaller hospitals (0-99 beds) were “somewhat overrepresented in the survey,” relative to their number nationwide, Merritt Hawkins said.

[email protected]

Physicians continue to be the major drivers of hospital revenue, and the average internist generated more revenue for hospitals in 2018 than ever before, according to a new survey by physician search firm Merritt Hawkins.

“The value of physician care is not only related to the quality of patient outcomes,” Travis Singleton, the company’s executive vice president, said in a written statement. “Physicians continue to drive the financial health and viability of hospitals, even in a health care system that is evolving towards value-based payments.”

Internists generated an average of nearly $2.68 million for their affiliated hospitals last year, which was up by 46% over 2015 (the survey is conducted every 3 years) and exceeded the previous high of $2.1 million in 2003, Merritt Hawkins reported.

Primary care physicians as a group averaged just over $2.13 million in revenue in 2018, compared with almost $2.45 million for specialists, which “suggests that emerging value-based delivery models have yet to inhibit the revenue-generating power of physician specialists,” the report said. Average revenue for all physicians in all 19 specialties in the survey was almost $2.38 million, an increase of 52% since Merritt Hawkins’ last survey.

The current survey was conducted from October through December of 2018 and is based on responses from 62 chief financial officers or other financial managers who represented 93 hospitals. Responses from smaller hospitals (0-99 beds) were “somewhat overrepresented in the survey,” relative to their number nationwide, Merritt Hawkins said.

[email protected]

Physicians continue to be the major drivers of hospital revenue, and the average internist generated more revenue for hospitals in 2018 than ever before, according to a new survey by physician search firm Merritt Hawkins.

“The value of physician care is not only related to the quality of patient outcomes,” Travis Singleton, the company’s executive vice president, said in a written statement. “Physicians continue to drive the financial health and viability of hospitals, even in a health care system that is evolving towards value-based payments.”

Internists generated an average of nearly $2.68 million for their affiliated hospitals last year, which was up by 46% over 2015 (the survey is conducted every 3 years) and exceeded the previous high of $2.1 million in 2003, Merritt Hawkins reported.

Primary care physicians as a group averaged just over $2.13 million in revenue in 2018, compared with almost $2.45 million for specialists, which “suggests that emerging value-based delivery models have yet to inhibit the revenue-generating power of physician specialists,” the report said. Average revenue for all physicians in all 19 specialties in the survey was almost $2.38 million, an increase of 52% since Merritt Hawkins’ last survey.

The current survey was conducted from October through December of 2018 and is based on responses from 62 chief financial officers or other financial managers who represented 93 hospitals. Responses from smaller hospitals (0-99 beds) were “somewhat overrepresented in the survey,” relative to their number nationwide, Merritt Hawkins said.

[email protected]

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.