User login
Muscle-related AEs reported in statin trial suggest ‘nocebo’ effect
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
FROM THE LANCET
Key clinical point: Patient reports of muscle-related adverse events related to statin use increases significantly after unblinding.
Major finding: The rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin than in nonusers in the nonblinded phase of a trial, compared with no significant difference between arms in the blinded phase.
Data source: The lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) involving 10,180 patients.
Disclosures: The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side effects of statin therapy. No other conflicts of interest were declared.
Time to therapy for gram-positive bacteremia reduced from 60 hours to 4 hours
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
AT PAS 2017
Key clinical point: Multiplex PCR and a revamped system of notification reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci from 60 hours to 4 hours within 6 months of implementation.
Major finding: and other gram-positive cocci-related infections.
Data source: A retrospective review of hospital records including patient data prior to and following implementation of multiplex PCR testing at one hospital.
Disclosures: The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
Using telemedicine to improve maternal safety
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001).
Data source: Results from 15 Utah hospitals that participated in the Obstetric Hemorrhage Collaborative.
Disclosures: The researchers reported having no financial disclosures.
More than one-third of genetic tests misordered, study finds
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Of genetic tests ordered by clinicians, 39% were deemed to be misordered.
Data source: A review of 114 genetic tests ordered over a 3-month period at a single center.
Disclosures: The researchers reported having no financial disclosures.
Adult vaccination is low, with minimal improvement in recent years
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
FROM MMWR
CAR T-cell data expected soon in mantle cell lymphoma
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
SUMMARY FROM CLINICALTRIALS.GOV
Isothiazolinone allergy frequent and underdiagnosed in children
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
FROM PEDIATRIC DERMATOLOGY
Key clinical point:
Major finding: There were 37 positive patch-test reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone.
Data source: An analysis of 1,056 patch-test results recorded in a database by clinicians during a 1-year period.
Disclosures: The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
G-CSF safe, but antibiotics are more concerning in SCLC
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
FROM ELCC
Key clinical point: Febrile neutropenia prophylaxis with G-CSF was safe, but prophylactic antibiotics were associated with worse overall survival in patients with limited stage–small cell lung cancer.
Major finding: Both median overall and progression-free survival were lower among patients who received prophylactic antibiotics. There were no differences in survival by G-CSF use.
Data source: Subanalysis of data on 487 patients in the phase III CONVERT trial comparing once-daily and twice daily radiation concurrent with chemotherapy in LS-SCLC.
Disclosures: The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
Should recent evidence of improved outcomes for neonates born during the periviable period change our approach to these deliveries?
EXPERT COMMENTARY
Pregnancy management when delivery appears to be imminent at 22 to 26 weeks’ gestation—a window defined as the periviable period—is among the most challenging situations that obstetricians face. Expert guidance exists both at a national level in a shared guideline from the American College of Obstetricians and Gynecologists and the Society of Maternal Fetal Medicine and, ideally, at a local level where teams of obstetricians and neonatologists have considered in their facility what represents best care
Among the most important yet often missing data points are outcomes of neonates born in the periviable period. Surveys suggest that obstetric care providers often underestimate the chance of survival following periviable delivery.2 Understanding and weighing anticipated outcomes inform decision making regarding management and planned obstetric and neonatal interventions, including plans for neonatal resuscitation.
Not surprisingly, perhaps, survival of periviable neonates has been linked clearly to willingness to undertake resuscitation.3 Yet decisions are not and should not be all about survival. Patients and providers want to know about short- and long-term morbidity, especially neurologic health, among survivors. Available collections of morbidity and mortality data, however, often are limited by whether all cases are captured or just those from specialized centers with particular management approaches, which outcomes are included and how they are defined, and the inevitable reality that the outcome of death “competes” with the outcome of neurologic development (that is, those neonates who die are not at risk for later abnormal neurologic outcome).
Given the need for more and better information, the data from a recent study by Younge and colleagues is especially welcome. The investigators reported on survival and neurologic outcome among more than 4,000 births between 22 and 24 weeks’ gestation at 11 centers in the United States.
Details of the study
The authors compared outcomes among three 3-year epochs between 2000 and 2011 and reported that the rate of survival without neurodevelopmental impairment increased over this period while the rate of survival with such impairment did not change. This argues that the observed overall increase in survival over these 12 years was not simply a tradeoff for life with significant impairment.
Within that overall message, however, the details of the data are important. Survival without neurodevelopmental impairment did improve from epoch 1 to epoch 3, but just from 16% to 20% (95% confidence interval [CI], 18–23; P = .001). Most neonates in the 2008–2011 epoch died (64%; 95% CI, 61–66; P<.001) or were severely impaired (16%; 95% CI, 14–18; P = .29). This led the authors to conclude that “despite improvements over time, the incidence of death, neurodevelopmental impairment, and other adverse outcomes remains high.” Examined separately, outcomes for infants born at 22 0/7 to 22 6/7 weeks’ gestation were very limited and unchanged over the 3 epochs studied, with death rates of 97% to 98% and survival without neurodevelopmental impairment of just 1%. In my own practice I do not encourage neonatal resuscitation, cesarean delivery, or many other interventions at less than 23 weeks’ gestation.
By contrast, the study showed that at 24 0/7 to 24 6/7 weeks’ gestation in the 2008–2011 epoch, 55% of neonates survived and, overall, 32% of infants survived without evidence of neurodevelopmental impairment at 18 to 22 months of age.
Related Article:
Is expectant management a safe alternative to immediate delivery in patients with PPROM close to term?
Study strengths and weaknesses
It is important to note that the definition of neurodevelopmental impairment used in the Younge study included only what many would classify as severe impairment, and survivors in this cohort “without” neurodevelopmental impairment may still have had important neurologic and other health concerns. In addition, the study did not track outcomes of the children at school age or beyond, when other developmental issues may become evident. As well, the study data may not be generalizable, for it included births from just 11 specialized centers, albeit a consortium accounting for 4% to 5% of periviable births in the United States.
Nevertheless, in supporting findings from other US and European analyses, these new data will help inform counseling conversations in the years to come. Such conversations should consider options for resuscitation, palliative care, and, at less than 24 weeks’ gestation, pregnancy termination. In individual cases these and many other decisions will be informed by both specific clinical circumstances—estimated fetal weight, fetal sex, presence of infection, use of antenatal steroids—and, perhaps most important, individual and family values and preferences. Despite these new data, managing periviable gestations will remain a great and important challenge.
--Jeffrey L. Ecker, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Obstetric Care Consensus No. 4: Periviable birth. Obstet Gynecol. 2016;127(6):e157-e169.
- Haywood JL, Goldenberg RL, Bronstein J, Nelson KG, Carlo WA. Comparison of perceived and actual rates of survival and freedom from handicap in premature infants. Am J Obstet Gynecol. 1994;171(2):432-439.
- Rysavy MA, Li L, Bell EF, et al; Eunice Kennedy Schriver National Institute of Child Health and Human Development Neonatal Research Unit. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med. 2015;372(19):1801-1811.
EXPERT COMMENTARY
Pregnancy management when delivery appears to be imminent at 22 to 26 weeks’ gestation—a window defined as the periviable period—is among the most challenging situations that obstetricians face. Expert guidance exists both at a national level in a shared guideline from the American College of Obstetricians and Gynecologists and the Society of Maternal Fetal Medicine and, ideally, at a local level where teams of obstetricians and neonatologists have considered in their facility what represents best care
Among the most important yet often missing data points are outcomes of neonates born in the periviable period. Surveys suggest that obstetric care providers often underestimate the chance of survival following periviable delivery.2 Understanding and weighing anticipated outcomes inform decision making regarding management and planned obstetric and neonatal interventions, including plans for neonatal resuscitation.
Not surprisingly, perhaps, survival of periviable neonates has been linked clearly to willingness to undertake resuscitation.3 Yet decisions are not and should not be all about survival. Patients and providers want to know about short- and long-term morbidity, especially neurologic health, among survivors. Available collections of morbidity and mortality data, however, often are limited by whether all cases are captured or just those from specialized centers with particular management approaches, which outcomes are included and how they are defined, and the inevitable reality that the outcome of death “competes” with the outcome of neurologic development (that is, those neonates who die are not at risk for later abnormal neurologic outcome).
Given the need for more and better information, the data from a recent study by Younge and colleagues is especially welcome. The investigators reported on survival and neurologic outcome among more than 4,000 births between 22 and 24 weeks’ gestation at 11 centers in the United States.
Details of the study
The authors compared outcomes among three 3-year epochs between 2000 and 2011 and reported that the rate of survival without neurodevelopmental impairment increased over this period while the rate of survival with such impairment did not change. This argues that the observed overall increase in survival over these 12 years was not simply a tradeoff for life with significant impairment.
Within that overall message, however, the details of the data are important. Survival without neurodevelopmental impairment did improve from epoch 1 to epoch 3, but just from 16% to 20% (95% confidence interval [CI], 18–23; P = .001). Most neonates in the 2008–2011 epoch died (64%; 95% CI, 61–66; P<.001) or were severely impaired (16%; 95% CI, 14–18; P = .29). This led the authors to conclude that “despite improvements over time, the incidence of death, neurodevelopmental impairment, and other adverse outcomes remains high.” Examined separately, outcomes for infants born at 22 0/7 to 22 6/7 weeks’ gestation were very limited and unchanged over the 3 epochs studied, with death rates of 97% to 98% and survival without neurodevelopmental impairment of just 1%. In my own practice I do not encourage neonatal resuscitation, cesarean delivery, or many other interventions at less than 23 weeks’ gestation.
By contrast, the study showed that at 24 0/7 to 24 6/7 weeks’ gestation in the 2008–2011 epoch, 55% of neonates survived and, overall, 32% of infants survived without evidence of neurodevelopmental impairment at 18 to 22 months of age.
Related Article:
Is expectant management a safe alternative to immediate delivery in patients with PPROM close to term?
Study strengths and weaknesses
It is important to note that the definition of neurodevelopmental impairment used in the Younge study included only what many would classify as severe impairment, and survivors in this cohort “without” neurodevelopmental impairment may still have had important neurologic and other health concerns. In addition, the study did not track outcomes of the children at school age or beyond, when other developmental issues may become evident. As well, the study data may not be generalizable, for it included births from just 11 specialized centers, albeit a consortium accounting for 4% to 5% of periviable births in the United States.
Nevertheless, in supporting findings from other US and European analyses, these new data will help inform counseling conversations in the years to come. Such conversations should consider options for resuscitation, palliative care, and, at less than 24 weeks’ gestation, pregnancy termination. In individual cases these and many other decisions will be informed by both specific clinical circumstances—estimated fetal weight, fetal sex, presence of infection, use of antenatal steroids—and, perhaps most important, individual and family values and preferences. Despite these new data, managing periviable gestations will remain a great and important challenge.
--Jeffrey L. Ecker, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
EXPERT COMMENTARY
Pregnancy management when delivery appears to be imminent at 22 to 26 weeks’ gestation—a window defined as the periviable period—is among the most challenging situations that obstetricians face. Expert guidance exists both at a national level in a shared guideline from the American College of Obstetricians and Gynecologists and the Society of Maternal Fetal Medicine and, ideally, at a local level where teams of obstetricians and neonatologists have considered in their facility what represents best care
Among the most important yet often missing data points are outcomes of neonates born in the periviable period. Surveys suggest that obstetric care providers often underestimate the chance of survival following periviable delivery.2 Understanding and weighing anticipated outcomes inform decision making regarding management and planned obstetric and neonatal interventions, including plans for neonatal resuscitation.
Not surprisingly, perhaps, survival of periviable neonates has been linked clearly to willingness to undertake resuscitation.3 Yet decisions are not and should not be all about survival. Patients and providers want to know about short- and long-term morbidity, especially neurologic health, among survivors. Available collections of morbidity and mortality data, however, often are limited by whether all cases are captured or just those from specialized centers with particular management approaches, which outcomes are included and how they are defined, and the inevitable reality that the outcome of death “competes” with the outcome of neurologic development (that is, those neonates who die are not at risk for later abnormal neurologic outcome).
Given the need for more and better information, the data from a recent study by Younge and colleagues is especially welcome. The investigators reported on survival and neurologic outcome among more than 4,000 births between 22 and 24 weeks’ gestation at 11 centers in the United States.
Details of the study
The authors compared outcomes among three 3-year epochs between 2000 and 2011 and reported that the rate of survival without neurodevelopmental impairment increased over this period while the rate of survival with such impairment did not change. This argues that the observed overall increase in survival over these 12 years was not simply a tradeoff for life with significant impairment.
Within that overall message, however, the details of the data are important. Survival without neurodevelopmental impairment did improve from epoch 1 to epoch 3, but just from 16% to 20% (95% confidence interval [CI], 18–23; P = .001). Most neonates in the 2008–2011 epoch died (64%; 95% CI, 61–66; P<.001) or were severely impaired (16%; 95% CI, 14–18; P = .29). This led the authors to conclude that “despite improvements over time, the incidence of death, neurodevelopmental impairment, and other adverse outcomes remains high.” Examined separately, outcomes for infants born at 22 0/7 to 22 6/7 weeks’ gestation were very limited and unchanged over the 3 epochs studied, with death rates of 97% to 98% and survival without neurodevelopmental impairment of just 1%. In my own practice I do not encourage neonatal resuscitation, cesarean delivery, or many other interventions at less than 23 weeks’ gestation.
By contrast, the study showed that at 24 0/7 to 24 6/7 weeks’ gestation in the 2008–2011 epoch, 55% of neonates survived and, overall, 32% of infants survived without evidence of neurodevelopmental impairment at 18 to 22 months of age.
Related Article:
Is expectant management a safe alternative to immediate delivery in patients with PPROM close to term?
Study strengths and weaknesses
It is important to note that the definition of neurodevelopmental impairment used in the Younge study included only what many would classify as severe impairment, and survivors in this cohort “without” neurodevelopmental impairment may still have had important neurologic and other health concerns. In addition, the study did not track outcomes of the children at school age or beyond, when other developmental issues may become evident. As well, the study data may not be generalizable, for it included births from just 11 specialized centers, albeit a consortium accounting for 4% to 5% of periviable births in the United States.
Nevertheless, in supporting findings from other US and European analyses, these new data will help inform counseling conversations in the years to come. Such conversations should consider options for resuscitation, palliative care, and, at less than 24 weeks’ gestation, pregnancy termination. In individual cases these and many other decisions will be informed by both specific clinical circumstances—estimated fetal weight, fetal sex, presence of infection, use of antenatal steroids—and, perhaps most important, individual and family values and preferences. Despite these new data, managing periviable gestations will remain a great and important challenge.
--Jeffrey L. Ecker, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Obstetric Care Consensus No. 4: Periviable birth. Obstet Gynecol. 2016;127(6):e157-e169.
- Haywood JL, Goldenberg RL, Bronstein J, Nelson KG, Carlo WA. Comparison of perceived and actual rates of survival and freedom from handicap in premature infants. Am J Obstet Gynecol. 1994;171(2):432-439.
- Rysavy MA, Li L, Bell EF, et al; Eunice Kennedy Schriver National Institute of Child Health and Human Development Neonatal Research Unit. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med. 2015;372(19):1801-1811.
- Obstetric Care Consensus No. 4: Periviable birth. Obstet Gynecol. 2016;127(6):e157-e169.
- Haywood JL, Goldenberg RL, Bronstein J, Nelson KG, Carlo WA. Comparison of perceived and actual rates of survival and freedom from handicap in premature infants. Am J Obstet Gynecol. 1994;171(2):432-439.
- Rysavy MA, Li L, Bell EF, et al; Eunice Kennedy Schriver National Institute of Child Health and Human Development Neonatal Research Unit. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med. 2015;372(19):1801-1811.
Non-cow’s milk associated with lower childhood height
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.
SAN FRANCISCO – Consumption of non-cow’s milk in early childhood is associated with decreased height, compared with consumption of cow’s milk by children in the same stage of life, a study has shown. The results call into question perceived health benefits of the consumption of non-cow’s milk in childhood.
“These findings are important for health care workers and parents in terms of optimal growth of children and the kind of milk needed to achieve that,” presenter Marie-Elssa Morency explained at the meeting of the Pediatric Academic Societies. Ms. Morency is a master’s student in the department of nutritional sciences at the University of Toronto.
Whether cow’s milk is a better source than non-cow’s milk of nutritional and caloric energy to a growing body has not been studied with rigor. Perceived health benefits of non-cow’s milk have led some parents to substitute cow’s milk with other types of milk for their children, Ms. Morency said.
To gain some clarity, the researchers looked at data from the TARGetKids! longitudinal cohort of children. The cohort is being followed into adolescence to link early life exposures to various physiological and developmental health problems. The present study looked at more than 5,000 healthy children aged 24-72 months. Any conditions that could affect growth were grounds for exclusion.
The primary exposure was the daily consumption of cow’s milk in 4,632 children or non-cow’s milk in 643 children. The typical number of 250-mL glasses of milk consumed per day was gleaned by a questionnaire completed by the parents. The primary outcome was height-for-age z score.
The two groups were similar at baseline in age, sex (slightly more than half were male), body mass index, and maternal height. Those who predominantly consumed cow’s milk averaged 2 cups per day. Some also consumed non-cow’s milk (about one glass per day). Those in the non-cow’s milk group consumed on average 1.4 cups per day, with cow’s milk consumption being rare.
The overall z-score was 0.1 (95% confidence interval [CI], –0.6 to 0.8). The groups differed in z-score, with a score of 0.2 (95% CI, –0.6 to 0.8) in the cow’s milk group and –0.04 (95% CI, –0.8 to 0.7) in the non-cow’s milk group. The resulting shorter height in those consuming non-cow’s milk was 0.42 cm (95% CI, –0.61 to –0.19) in a univariate analysis (P less than .001). A multivariate analysis that adjusted for age, sex, maternal ethnicity, maternal height, z-score, and neighborhood income revealed a significant difference in the same group of 0.31 cm (95% CI, –0.50 to –0.11; P less than .001).
The reduced consumption of cow’s milk in the non-cow’s milk group was identified as a partial mediator of the association between non-cow’s milk consumption and height. Putting the results into context, Ms. Morency explained that a 3-year-old child typically drinking 3 cups of non-cow’s milk each day (about twice the average in this study) would be 1.5 cm shorter than a similar child drinking the same amount of cow’s milk each day.
The literature shows that height children achieve during childhood is an important benchmark of growth and development, adequate nutrition, and pending obesity. Shorter-than average children can often be shorter than average in height as adults, which has been linked with increased risk of type 2 diabetes, gestational diabetes, coronary heart disease, and hypertension.
Diet influences height: Reduced calories and nutrients in an inadequate diet hinder growth, Ms. Morency noted. Cow’s milk delivers more protein, fat, vitamins, minerals, and calories than do non-cow’s milk formulations, such as almond milk and soy milk, she said.
“While non-cow’s milk consumption in childhood may have other health benefits, increased height does not appear to be one of them,” said Ms. Morency.
Study strengths include the relatively large sample size, statistical rigor, and consistent findings with prior studies. Limitations include the cross-sectional design that rules out any conclusions about direct cause, and the use of questionnaire data, which inherently comes with problems of report and recall bias.
A causal connection awaits randomized controlled trials.
The University of Toronto sponsored the study, which was funded by the Canadian Institutes for Health Research. Ms. Morency reported having no financial disclosures.