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Group B strep: Short-course IV controls infant infection
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
FROM PEDIATRICS
Key clinical point: Courses of IV antibiotics shorter than recommended for group B streptococcus bacteremia yield low rates of recurrence and treatment failure.
Major finding: Three children treated with a shorter IV duration had recurrence of group B strep, compared with 14 children in a longer treatment group (1.8% vs. 2.3%).
Study details: The data come from a multicenter retrospective cohort study of 775 infants aged 7 days to 4 months.
Disclosures: The researchers had no financial conflicts to disclose.
Source: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0345.
Be proactive with prophylaxis to tame VTE
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
FROM WORLD THROMBOSIS DAY 2018 WEBINAR
Task force advises behavioral intervention for obese adults
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
FROM JAMA
Brain mapping takes next step toward precision psychiatry
Brain mapping patterns varied with clinical mental health diagnoses in a study of 218 patients with schizophrenia spectrum disorders.
“Psychiatry is now the last area of medicine in which diseases are diagnosed solely on the basis of symptoms, and biomarkers to assist treatment remain to be developed,” wrote Thomas Wolfers of Radboud University, Nijmegen, the Netherlands, and his colleagues. They also said schizophrenia and bipolar disorder “are excellent examples of highly heterogeneous mental disorders.”
To explore brain structure homogeneity, the researchers used brain scans and mapping models to compare results in 218 adults aged 18-65 years with schizophrenia disorders (163 with schizophrenia and 190 with bipolar disorder) and 256 healthy controls. Demographics were similar between the groups.
The MRI data showed that the same abnormalities in more than 2% of patients with the same disorder occurred in very few loci. Schizophrenia patients showed significantly reduced gray matter in the frontal, cerebellar, and temporal regions; most bipolar patients showed changes in the cerebellar region.
The researchers identified extreme deviations across patients and controls in gray and white matter.
In gray matter, schizophrenia patients had a significantly higher percentage of extreme negative deviations across voxels (0.9% of voxels), compared with both bipolar patients and healthy controls (0.24% and 0.23%, respectively).
In white matter, a similar pattern emerged; schizophrenia patients had a significantly higher percentage of extreme negative deviations (0.62%), compared with healthy controls and bipolar patients (0.25% and 0.41%, respectively). In addition, extreme positive deviations were significantly higher among the controls (1.14% of voxels), compared with schizophrenia and bipolar patients (0.83% for both).
The findings support data from previous studies suggesting reduced cortical volume in schizophrenia patients, compared with healthy controls and bipolar disorder patients, the researchers noted.
“In this study, patients with schizophrenia and bipolar disorder differed extremely on an individual level; the lack of substantial overlap among patients in terms of extreme deviations from the normative model is evidence of the high degree of biological heterogeneity in both disorders,” wrote Mr. Wolfers and his colleagues.
The main limitations of the study were the inability to control for confounding variables and to make conclusions about causality, the researchers said. However, the absence of overlap in patients with the same disorder supports the use of brain mapping to study individual pathophysiologic signatures in schizophrenia and bipolar disorder patients, they concluded.
Mr. Wolfers had no financial conflicts to disclose. The study was supported by grants from multiple organizations, including the Netherlands Organisation for Scientific Research and the Wellcome Trust U.K. Strategic Award.
SOURCE: Wolfers T et al. JAMA Psychiatry. 2018. doi: 10.1001/jamapsychiatry.2018.2467.
A growing body of evidence suggests that “conventional psychiatric diagnoses of serious mental illness (SMI), when tested, do not show a common biology,” wrote Carol A. Tamminga, MD, and Elena I. Ivleva, MD, PhD, in an accompanying editorial. The editorialists noted the work of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium to identify subtype disease clusters.
However, they wrote: “We question whether these biotype structures represent disease groups as opposed to mere brain biomarker clusters. Dr. Tamminga and Dr. Ivleva also expressed concern about whether biologically based subgroups would be clinically useful and questioned what evidence would be needed to accept such subtypes as disease subgroups.
Their ideas for further exploration included identifying a characteristic genetic fingerprint to help determine a common pathophysiology. In addition, “a disorder clustered by biological features might also show a distinctive pharmacological profile,” they wrote.
Next steps include making severe mental illness into a condition diagnosable based on biomarkers that also can serve as a foundation for treatment, which would be “a revolution in our ability to understand and treat complex brain disorders,” they noted (JAMA Psychiatry. 2018 Oct. doi: 10.1001/jamapsychiatry.2018.2451).
Dr. Tamminga and Dr. Ivleva are affiliated with the University of Texas, Dallas. Both of them serve as researchers with the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium and reported funding from the National Institute for Mental Health.
A growing body of evidence suggests that “conventional psychiatric diagnoses of serious mental illness (SMI), when tested, do not show a common biology,” wrote Carol A. Tamminga, MD, and Elena I. Ivleva, MD, PhD, in an accompanying editorial. The editorialists noted the work of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium to identify subtype disease clusters.
However, they wrote: “We question whether these biotype structures represent disease groups as opposed to mere brain biomarker clusters. Dr. Tamminga and Dr. Ivleva also expressed concern about whether biologically based subgroups would be clinically useful and questioned what evidence would be needed to accept such subtypes as disease subgroups.
Their ideas for further exploration included identifying a characteristic genetic fingerprint to help determine a common pathophysiology. In addition, “a disorder clustered by biological features might also show a distinctive pharmacological profile,” they wrote.
Next steps include making severe mental illness into a condition diagnosable based on biomarkers that also can serve as a foundation for treatment, which would be “a revolution in our ability to understand and treat complex brain disorders,” they noted (JAMA Psychiatry. 2018 Oct. doi: 10.1001/jamapsychiatry.2018.2451).
Dr. Tamminga and Dr. Ivleva are affiliated with the University of Texas, Dallas. Both of them serve as researchers with the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium and reported funding from the National Institute for Mental Health.
A growing body of evidence suggests that “conventional psychiatric diagnoses of serious mental illness (SMI), when tested, do not show a common biology,” wrote Carol A. Tamminga, MD, and Elena I. Ivleva, MD, PhD, in an accompanying editorial. The editorialists noted the work of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium to identify subtype disease clusters.
However, they wrote: “We question whether these biotype structures represent disease groups as opposed to mere brain biomarker clusters. Dr. Tamminga and Dr. Ivleva also expressed concern about whether biologically based subgroups would be clinically useful and questioned what evidence would be needed to accept such subtypes as disease subgroups.
Their ideas for further exploration included identifying a characteristic genetic fingerprint to help determine a common pathophysiology. In addition, “a disorder clustered by biological features might also show a distinctive pharmacological profile,” they wrote.
Next steps include making severe mental illness into a condition diagnosable based on biomarkers that also can serve as a foundation for treatment, which would be “a revolution in our ability to understand and treat complex brain disorders,” they noted (JAMA Psychiatry. 2018 Oct. doi: 10.1001/jamapsychiatry.2018.2451).
Dr. Tamminga and Dr. Ivleva are affiliated with the University of Texas, Dallas. Both of them serve as researchers with the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium and reported funding from the National Institute for Mental Health.
Brain mapping patterns varied with clinical mental health diagnoses in a study of 218 patients with schizophrenia spectrum disorders.
“Psychiatry is now the last area of medicine in which diseases are diagnosed solely on the basis of symptoms, and biomarkers to assist treatment remain to be developed,” wrote Thomas Wolfers of Radboud University, Nijmegen, the Netherlands, and his colleagues. They also said schizophrenia and bipolar disorder “are excellent examples of highly heterogeneous mental disorders.”
To explore brain structure homogeneity, the researchers used brain scans and mapping models to compare results in 218 adults aged 18-65 years with schizophrenia disorders (163 with schizophrenia and 190 with bipolar disorder) and 256 healthy controls. Demographics were similar between the groups.
The MRI data showed that the same abnormalities in more than 2% of patients with the same disorder occurred in very few loci. Schizophrenia patients showed significantly reduced gray matter in the frontal, cerebellar, and temporal regions; most bipolar patients showed changes in the cerebellar region.
The researchers identified extreme deviations across patients and controls in gray and white matter.
In gray matter, schizophrenia patients had a significantly higher percentage of extreme negative deviations across voxels (0.9% of voxels), compared with both bipolar patients and healthy controls (0.24% and 0.23%, respectively).
In white matter, a similar pattern emerged; schizophrenia patients had a significantly higher percentage of extreme negative deviations (0.62%), compared with healthy controls and bipolar patients (0.25% and 0.41%, respectively). In addition, extreme positive deviations were significantly higher among the controls (1.14% of voxels), compared with schizophrenia and bipolar patients (0.83% for both).
The findings support data from previous studies suggesting reduced cortical volume in schizophrenia patients, compared with healthy controls and bipolar disorder patients, the researchers noted.
“In this study, patients with schizophrenia and bipolar disorder differed extremely on an individual level; the lack of substantial overlap among patients in terms of extreme deviations from the normative model is evidence of the high degree of biological heterogeneity in both disorders,” wrote Mr. Wolfers and his colleagues.
The main limitations of the study were the inability to control for confounding variables and to make conclusions about causality, the researchers said. However, the absence of overlap in patients with the same disorder supports the use of brain mapping to study individual pathophysiologic signatures in schizophrenia and bipolar disorder patients, they concluded.
Mr. Wolfers had no financial conflicts to disclose. The study was supported by grants from multiple organizations, including the Netherlands Organisation for Scientific Research and the Wellcome Trust U.K. Strategic Award.
SOURCE: Wolfers T et al. JAMA Psychiatry. 2018. doi: 10.1001/jamapsychiatry.2018.2467.
Brain mapping patterns varied with clinical mental health diagnoses in a study of 218 patients with schizophrenia spectrum disorders.
“Psychiatry is now the last area of medicine in which diseases are diagnosed solely on the basis of symptoms, and biomarkers to assist treatment remain to be developed,” wrote Thomas Wolfers of Radboud University, Nijmegen, the Netherlands, and his colleagues. They also said schizophrenia and bipolar disorder “are excellent examples of highly heterogeneous mental disorders.”
To explore brain structure homogeneity, the researchers used brain scans and mapping models to compare results in 218 adults aged 18-65 years with schizophrenia disorders (163 with schizophrenia and 190 with bipolar disorder) and 256 healthy controls. Demographics were similar between the groups.
The MRI data showed that the same abnormalities in more than 2% of patients with the same disorder occurred in very few loci. Schizophrenia patients showed significantly reduced gray matter in the frontal, cerebellar, and temporal regions; most bipolar patients showed changes in the cerebellar region.
The researchers identified extreme deviations across patients and controls in gray and white matter.
In gray matter, schizophrenia patients had a significantly higher percentage of extreme negative deviations across voxels (0.9% of voxels), compared with both bipolar patients and healthy controls (0.24% and 0.23%, respectively).
In white matter, a similar pattern emerged; schizophrenia patients had a significantly higher percentage of extreme negative deviations (0.62%), compared with healthy controls and bipolar patients (0.25% and 0.41%, respectively). In addition, extreme positive deviations were significantly higher among the controls (1.14% of voxels), compared with schizophrenia and bipolar patients (0.83% for both).
The findings support data from previous studies suggesting reduced cortical volume in schizophrenia patients, compared with healthy controls and bipolar disorder patients, the researchers noted.
“In this study, patients with schizophrenia and bipolar disorder differed extremely on an individual level; the lack of substantial overlap among patients in terms of extreme deviations from the normative model is evidence of the high degree of biological heterogeneity in both disorders,” wrote Mr. Wolfers and his colleagues.
The main limitations of the study were the inability to control for confounding variables and to make conclusions about causality, the researchers said. However, the absence of overlap in patients with the same disorder supports the use of brain mapping to study individual pathophysiologic signatures in schizophrenia and bipolar disorder patients, they concluded.
Mr. Wolfers had no financial conflicts to disclose. The study was supported by grants from multiple organizations, including the Netherlands Organisation for Scientific Research and the Wellcome Trust U.K. Strategic Award.
SOURCE: Wolfers T et al. JAMA Psychiatry. 2018. doi: 10.1001/jamapsychiatry.2018.2467.
FROM JAMA PSYCHIATRY
Key clinical point: Technology that allows for brain mapping offers a framework for greater use of precision medicine in psychiatry.
Major finding: Few brain loci showed extreme deviations in more than 2% of patients with schizophrenia disorders in a brain mapping model.
Study details: The data come from MRI scans of 218 patients with schizophrenia or bipolar disorder and 256 healthy controls.
Disclosures: Mr. Wolfers had no financial conflicts to disclose. The study was supported by grants from multiple organizations, including the Netherlands Organisation for Scientific Research and the Wellcome Trust U.K. Strategic Award.
Source: Wolfers T et al. JAMA Psychiatry. 2018. doi: 10.1001/jamapsychiatry.2018.2467.
Third trimester Tdap vaccination raises antibodies in newborns
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
FROM JAMA
Key clinical point:
Major finding: The geometric mean concentration of neonatal cord pertussis toxin antibodies was 47.3 IU/mL among newborns exposed to Tdap, compared with 12.9 IU/mL among unexposed (P less than .001).
Study details: The data come from an observational study of 626 pregnancies.
Disclosures: The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
Source: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
Consider ART for younger endometriosis patients
but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.
Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.
In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.
Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.
“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.
They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).
The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.
The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.
SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.
but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.
Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.
In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.
Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.
“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.
They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).
The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.
The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.
SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.
but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.
Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.
In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.
Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.
“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.
They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).
The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.
The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.
SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.
FROM THE JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
Key clinical point: ART was more effective than was non-ART against infertility in women with endometriosis, especially among younger women.
Major finding: The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%).
Study details: A retrospective study of 1,864 infertile women in Japan, including 288 with advanced endometriosis.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.
Source: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.
IL inhibitor options move psoriasis treatment forward
Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.
“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.
Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).
Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.
Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.
For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.
Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.
Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.
Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.
What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.
IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).
For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.
In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.
Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.
The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.
Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.
“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.
Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).
Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.
Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.
For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.
Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.
Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.
Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.
What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.
IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).
For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.
In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.
Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.
The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.
Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.
“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.
Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).
Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.
Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.
For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.
Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.
Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.
Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.
What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.
IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).
For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.
In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.
Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.
The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.
FROM THE COASTAL DERMATOLOGY SYMPOSIUM
Obesity in early childhood promotes obese adolescence
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Of children who were obese at age 4 years, 83% were overweight or obese in adolescence.
Study details: The data come from a retrospective study of 51,505 children in Germany.
Disclosures: The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
Source: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Zoledronate reduces fracture risk in elderly women with osteopenia
Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.
The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.
Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”
The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.
Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.
Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.
The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.
The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.
The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.
Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.
SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.
This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.
Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.
In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.
Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.
This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.
Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.
In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.
Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.
This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.
Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.
In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.
Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.
Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.
The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.
Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”
The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.
Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.
Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.
The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.
The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.
The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.
Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.
SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.
Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.
The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.
Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”
The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.
Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.
Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.
The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.
The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.
The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.
Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.
SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.
REPORTING FROM ASBMR
Key clinical point: Vertebral and nonvertebral fracture risk was significantly lower in osteopenic women who received zoledronate, compared with those who received a placebo.
Major finding: Fragility fractures occurred in 122 women in a zoledronate group and 190 women in a placebo group. The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.
Study details: A 6-year randomized, double-blind trial of 2,000 women aged 65 years and older with osteopenia.
Disclosures: The study was supported in part by grants from the Health Research Council of New Zealand; Novartis provided the medication. Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.
Source: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.
Maximize well-woman visits for preventive services, counseling
A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.
“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.
Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.
The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.
“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.
Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.
The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.
“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.
“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”
Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.
The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.
The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.
“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.
Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.
The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.
“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.
Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.
The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.
“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.
“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”
Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.
The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.
The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.
“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.
Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.
The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.
“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.
Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.
The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.
“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.
“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”
Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.
The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.
The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
FROM OBSTETRICS & GYNECOLOGY