Early enterovirus infections could be an underlying cause of celiac disease, according to a case-control study of Norwegian children with an at-risk genotype.

designer491/Thinkstock

“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.

From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.

Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.

The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”

The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.

SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.

Early enterovirus infections could be an underlying cause of celiac disease, according to a case-control study of Norwegian children with an at-risk genotype.

designer491/Thinkstock

“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.

From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.

Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.

The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”

The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.

SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.

Early enterovirus infections could be an underlying cause of celiac disease, according to a case-control study of Norwegian children with an at-risk genotype.

designer491/Thinkstock

“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.

From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.

Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.

The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”

The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.

SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.

LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.

On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”

The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.

Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).

Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).

“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”

In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”

Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.

At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”

The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.

SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.

LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.

On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”

The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.

Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).

Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).

“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”

In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”

Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.

At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”

The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.

SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.

LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.

On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”

The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.

Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).

Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).

“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”

In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”

Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.

At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”

The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.

SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.

LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.

Kari Oakes/MDedge News

For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).

Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.

By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).

“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.

Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.

The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.

The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.

Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.

The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.

Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.

A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.

The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m².

Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.

The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).

The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.

Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.

Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.

The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.

“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.

Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).

The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).

For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).

Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.

Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.

“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.

Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.

koakes@mdedge.com

SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.

LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.

Kari Oakes/MDedge News

For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).

Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.

By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).

“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.

Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.

The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.

The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.

Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.

The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.

Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.

A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.

The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m².

Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.

The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).

The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.

Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.

Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.

The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.

“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.

Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).

The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).

For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).

Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.

Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.

“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.

Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.

koakes@mdedge.com

SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.

LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.

Kari Oakes/MDedge News

For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).

Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.

By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).

“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.

Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.

The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.

The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.

Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.

The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.

Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.

A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.

The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m².

Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.

The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).

The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.

Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.

Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.

The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.

“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.

Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).

The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).

For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).

Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.

Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.

“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.

Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.

koakes@mdedge.com

SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.

Most skin eruptions in patients who are taking antiepileptic drugs are relatively benign, but with close supervision, some patients with epilepsy may continue treatment. Also today, adherence to statins is lower among younger patients, women, and minorities, the flu season rages on, and how medication-assisted treatment impacts pregnant women with opioid use disorder.

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Most skin eruptions in patients who are taking antiepileptic drugs are relatively benign, but with close supervision, some patients with epilepsy may continue treatment. Also today, adherence to statins is lower among younger patients, women, and minorities, the flu season rages on, and how medication-assisted treatment impacts pregnant women with opioid use disorder.

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Apple Podcasts
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Spotify
 

Most skin eruptions in patients who are taking antiepileptic drugs are relatively benign, but with close supervision, some patients with epilepsy may continue treatment. Also today, adherence to statins is lower among younger patients, women, and minorities, the flu season rages on, and how medication-assisted treatment impacts pregnant women with opioid use disorder.

Amazon Alexa
Apple Podcasts
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Spotify
 

Bag-mask ventilation during tracheal intubation may significantly improve oxygen saturation and reduce the risk of severe hypoxemia, according to data presented at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

ivan68/Getty Images

A multicenter study, published simultaneously in the Feb. 18 issue of the New England Journal of Medicine, randomized 401 critically-ill patients in the ICU who were undergoing tracheal intubation to receive either ventilation with a bag-mask device during induction for intubation or no ventilation.

The median lowest oxygen saturation between induction and 2 minutes after intubation was 96% in the bag-mask ventilated patients and 93% in the no-ventilation group, representing a 4.7% difference after adjusting for prespecified covariates (P = .01).

In a post-hoc analysis that adjusted for other factors such as the provision of preoxygenation, the preoxygenation device, pneumonia, and gastrointestinal bleeding, there was a 5.2% difference between the two groups in median lowest oxygen saturation, favoring the bag-mask group.

Bag-mask ventilation was also associated with almost a halving in the incidence of severe hypoxemia – defined as an oxygen saturation below 80% – compared with no-ventilation (10.9% vs. 22.8%; relative risk = 0.48). There was also a lower incidence of patients with an oxygen saturation below 90% and below 70% in the bag-mask ventilation group, compared with the no-ventilation group.

Overall, the median decrease in oxygen saturation from induction to the lowest point was 1% in the bag-mask group, and 5% in the no-ventilation group.

The study saw no effects of factors such as body-mass index, operator experience, or Acute Physiology and Chronic Health Evaluation (APACHE II) score. The patients had a median age of 60 years, about half had sepsis or septic shock, and close to 60% had hypoxemic respiratory failure as an indication for tracheal intubation.

SOURCE: Casey J et al. N Engl J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1812405

Bag-mask ventilation during tracheal intubation may significantly improve oxygen saturation and reduce the risk of severe hypoxemia, according to data presented at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

ivan68/Getty Images

A multicenter study, published simultaneously in the Feb. 18 issue of the New England Journal of Medicine, randomized 401 critically-ill patients in the ICU who were undergoing tracheal intubation to receive either ventilation with a bag-mask device during induction for intubation or no ventilation.

The median lowest oxygen saturation between induction and 2 minutes after intubation was 96% in the bag-mask ventilated patients and 93% in the no-ventilation group, representing a 4.7% difference after adjusting for prespecified covariates (P = .01).

In a post-hoc analysis that adjusted for other factors such as the provision of preoxygenation, the preoxygenation device, pneumonia, and gastrointestinal bleeding, there was a 5.2% difference between the two groups in median lowest oxygen saturation, favoring the bag-mask group.

Bag-mask ventilation was also associated with almost a halving in the incidence of severe hypoxemia – defined as an oxygen saturation below 80% – compared with no-ventilation (10.9% vs. 22.8%; relative risk = 0.48). There was also a lower incidence of patients with an oxygen saturation below 90% and below 70% in the bag-mask ventilation group, compared with the no-ventilation group.

Overall, the median decrease in oxygen saturation from induction to the lowest point was 1% in the bag-mask group, and 5% in the no-ventilation group.

The study saw no effects of factors such as body-mass index, operator experience, or Acute Physiology and Chronic Health Evaluation (APACHE II) score. The patients had a median age of 60 years, about half had sepsis or septic shock, and close to 60% had hypoxemic respiratory failure as an indication for tracheal intubation.

SOURCE: Casey J et al. N Engl J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1812405

Bag-mask ventilation during tracheal intubation may significantly improve oxygen saturation and reduce the risk of severe hypoxemia, according to data presented at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.

ivan68/Getty Images

A multicenter study, published simultaneously in the Feb. 18 issue of the New England Journal of Medicine, randomized 401 critically-ill patients in the ICU who were undergoing tracheal intubation to receive either ventilation with a bag-mask device during induction for intubation or no ventilation.

The median lowest oxygen saturation between induction and 2 minutes after intubation was 96% in the bag-mask ventilated patients and 93% in the no-ventilation group, representing a 4.7% difference after adjusting for prespecified covariates (P = .01).

In a post-hoc analysis that adjusted for other factors such as the provision of preoxygenation, the preoxygenation device, pneumonia, and gastrointestinal bleeding, there was a 5.2% difference between the two groups in median lowest oxygen saturation, favoring the bag-mask group.

Bag-mask ventilation was also associated with almost a halving in the incidence of severe hypoxemia – defined as an oxygen saturation below 80% – compared with no-ventilation (10.9% vs. 22.8%; relative risk = 0.48). There was also a lower incidence of patients with an oxygen saturation below 90% and below 70% in the bag-mask ventilation group, compared with the no-ventilation group.

Overall, the median decrease in oxygen saturation from induction to the lowest point was 1% in the bag-mask group, and 5% in the no-ventilation group.

The study saw no effects of factors such as body-mass index, operator experience, or Acute Physiology and Chronic Health Evaluation (APACHE II) score. The patients had a median age of 60 years, about half had sepsis or septic shock, and close to 60% had hypoxemic respiratory failure as an indication for tracheal intubation.

SOURCE: Casey J et al. N Engl J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1812405

Over-the-counter (OTC) insulin is chiefly purchased at Walmart pharmacies, likely because their brand is considerably less expensive than the OTC insulin sold elsewhere, according to a national survey of pharmacy employees.

The survey was undertaken by Jennifer N. Goldstein, MD, of Christiana Care Health System in Newark, Del., and her colleagues and published online Feb. 18 in JAMA Internal Medicine.

iStock/ThinkStock

As Walmart does not make its sales data public, Dr. Goldstein and her colleagues conducted a national telephone-based survey of Walmart and chain pharmacies in the 49 states where OTC insulin is available. They administered a five-item questionnaire that sought to determine the frequency of OTC insulin sales.

Of the 561 pharmacies that completed the questionnaire, 500 (89.1%) responded that they did sell OTC insulin; this included 284 of 292 Walmart pharmacies. Among those Walmart pharmacies, 247 (87%) said sales of OTC insulin occurred daily; 31 (10.9%) sold it weekly; and 3 (1.1%) sold it monthly.

The chains (CVS, Walgreens, Rite Aid) reported far less frequent sales of OTC insulin; 100 out of 216 (46.3%) pharmacies said they made sales only “a few times a year,” and none reported daily sales.

A majority of respondents (54.9%) also answered yes when asked if they believed patients purchased OTC insulin because they could not afford the copayment on prescription insulin; 70.1% of those positive responses came from Walmart pharmacies.

The coauthors acknowledged that their survey represents the impressions of pharmacy employees as opposed to actual sales data. The numbers, however, do “support an estimate of daily sales of more than 18,000 vials of over-the-counter insulin at Walmart pharmacies.” As for next steps, they noted that “further studies should explore clinical and safety outcomes related to the use of over-the-counter insulin.”

One author was supported by a grant from the National Institutes of Health. No conflicts of interest were reported.

SOURCE: Goldstein JN et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7279

Over-the-counter (OTC) insulin is chiefly purchased at Walmart pharmacies, likely because their brand is considerably less expensive than the OTC insulin sold elsewhere, according to a national survey of pharmacy employees.

The survey was undertaken by Jennifer N. Goldstein, MD, of Christiana Care Health System in Newark, Del., and her colleagues and published online Feb. 18 in JAMA Internal Medicine.

iStock/ThinkStock

As Walmart does not make its sales data public, Dr. Goldstein and her colleagues conducted a national telephone-based survey of Walmart and chain pharmacies in the 49 states where OTC insulin is available. They administered a five-item questionnaire that sought to determine the frequency of OTC insulin sales.

Of the 561 pharmacies that completed the questionnaire, 500 (89.1%) responded that they did sell OTC insulin; this included 284 of 292 Walmart pharmacies. Among those Walmart pharmacies, 247 (87%) said sales of OTC insulin occurred daily; 31 (10.9%) sold it weekly; and 3 (1.1%) sold it monthly.

The chains (CVS, Walgreens, Rite Aid) reported far less frequent sales of OTC insulin; 100 out of 216 (46.3%) pharmacies said they made sales only “a few times a year,” and none reported daily sales.

A majority of respondents (54.9%) also answered yes when asked if they believed patients purchased OTC insulin because they could not afford the copayment on prescription insulin; 70.1% of those positive responses came from Walmart pharmacies.

The coauthors acknowledged that their survey represents the impressions of pharmacy employees as opposed to actual sales data. The numbers, however, do “support an estimate of daily sales of more than 18,000 vials of over-the-counter insulin at Walmart pharmacies.” As for next steps, they noted that “further studies should explore clinical and safety outcomes related to the use of over-the-counter insulin.”

One author was supported by a grant from the National Institutes of Health. No conflicts of interest were reported.

SOURCE: Goldstein JN et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7279

Over-the-counter (OTC) insulin is chiefly purchased at Walmart pharmacies, likely because their brand is considerably less expensive than the OTC insulin sold elsewhere, according to a national survey of pharmacy employees.

The survey was undertaken by Jennifer N. Goldstein, MD, of Christiana Care Health System in Newark, Del., and her colleagues and published online Feb. 18 in JAMA Internal Medicine.

iStock/ThinkStock

As Walmart does not make its sales data public, Dr. Goldstein and her colleagues conducted a national telephone-based survey of Walmart and chain pharmacies in the 49 states where OTC insulin is available. They administered a five-item questionnaire that sought to determine the frequency of OTC insulin sales.

Of the 561 pharmacies that completed the questionnaire, 500 (89.1%) responded that they did sell OTC insulin; this included 284 of 292 Walmart pharmacies. Among those Walmart pharmacies, 247 (87%) said sales of OTC insulin occurred daily; 31 (10.9%) sold it weekly; and 3 (1.1%) sold it monthly.

The chains (CVS, Walgreens, Rite Aid) reported far less frequent sales of OTC insulin; 100 out of 216 (46.3%) pharmacies said they made sales only “a few times a year,” and none reported daily sales.

A majority of respondents (54.9%) also answered yes when asked if they believed patients purchased OTC insulin because they could not afford the copayment on prescription insulin; 70.1% of those positive responses came from Walmart pharmacies.

The coauthors acknowledged that their survey represents the impressions of pharmacy employees as opposed to actual sales data. The numbers, however, do “support an estimate of daily sales of more than 18,000 vials of over-the-counter insulin at Walmart pharmacies.” As for next steps, they noted that “further studies should explore clinical and safety outcomes related to the use of over-the-counter insulin.”

One author was supported by a grant from the National Institutes of Health. No conflicts of interest were reported.

SOURCE: Goldstein JN et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7279

First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.

In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”

The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).

jremaly@mdedge.com

SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905

First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.

In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”

The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).

jremaly@mdedge.com

SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905

First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.

In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”

The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).

jremaly@mdedge.com

SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905

Transgender individuals receiving hormone therapy may have a greater risk of cardiovascular events such as stroke, venous thromboembolism, and myocardial infarction when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.

“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.

They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*

Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).

The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.

There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).

The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).

In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.

The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.

The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.

The study had no specific funding, and the authors reported no relevant conflicts of interest.

SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584

*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate. 

Transgender individuals receiving hormone therapy may have a greater risk of cardiovascular events such as stroke, venous thromboembolism, and myocardial infarction when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.

“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.

They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*

Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).

The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.

There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).

The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).

In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.

The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.

The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.

The study had no specific funding, and the authors reported no relevant conflicts of interest.

SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584

*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate. 

Transgender individuals receiving hormone therapy may have a greater risk of cardiovascular events such as stroke, venous thromboembolism, and myocardial infarction when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.

“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.

They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*

Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).

The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.

There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).

The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).

In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.

The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.

The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.

The study had no specific funding, and the authors reported no relevant conflicts of interest.

SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584

*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate. 

Does adherence to a Mediterranean diet reduce the risk of Parkinson’s disease? ‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
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Does adherence to a Mediterranean diet reduce the risk of Parkinson’s disease? ‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Does adherence to a Mediterranean diet reduce the risk of Parkinson’s disease? ‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.