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Timely epinephrine for pediatric in-hospital cardiac arrest
Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published online Aug. 25 in JAMA.
For the approximately 16,000 U.S. children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.
It is highly unlikely that any such study will ever be done, given the ethical considerations, so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period, said Dr. Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, and the department of anesthesiology at Aarhus (Denmark) University and his associates.
All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.
Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (relative risk, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).
In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr. Andersen and his associates said (JAMA. 2015 Aug 25. doi: 10.1001/jama.2015.9678).
These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.
The findings by Dr. Andersen and his associates provide fairly strong evidence that following current guidelines for epinephrine timing is best practice, supporting an AHA class I strength of recommendation.
The investigators are correct to note that observational data cannot establish causality. Almost all of these cardiac arrests were witnessed; approximately two-thirds occurred in the pediatric intensive care unit, operating room, or postanesthesia setting; and half of the patients were receiving mechanical ventilation. So it is possible that the link between timing of epinephrine and outcomes may simply reflect factors such as the circumstances of the cardiac arrest, the presence of an airway and intravenous access, or the quality of chest compressions.
Dr. Robert C. Tasker and Dr. Adriennne G. Randolph are with the division of critical care medicine, department of anesthesia, perioperative, and pain medicine at Boston Children’s Hospital and the department of anesthesia at Harvard Medical School. Dr. Tasker is also with the department of neurology at both institutions and Dr. Randolph is also with the department of pediatrics at Harvard. Both authors reported having no relevant financial conflicts of interest. Dr. Tasker and Dr. Randolph made these remarks in an accompanying editorial (JAMA. 2015;314:776-7. doi: 10.1001/jama.2015.9527).
The findings by Dr. Andersen and his associates provide fairly strong evidence that following current guidelines for epinephrine timing is best practice, supporting an AHA class I strength of recommendation.
The investigators are correct to note that observational data cannot establish causality. Almost all of these cardiac arrests were witnessed; approximately two-thirds occurred in the pediatric intensive care unit, operating room, or postanesthesia setting; and half of the patients were receiving mechanical ventilation. So it is possible that the link between timing of epinephrine and outcomes may simply reflect factors such as the circumstances of the cardiac arrest, the presence of an airway and intravenous access, or the quality of chest compressions.
Dr. Robert C. Tasker and Dr. Adriennne G. Randolph are with the division of critical care medicine, department of anesthesia, perioperative, and pain medicine at Boston Children’s Hospital and the department of anesthesia at Harvard Medical School. Dr. Tasker is also with the department of neurology at both institutions and Dr. Randolph is also with the department of pediatrics at Harvard. Both authors reported having no relevant financial conflicts of interest. Dr. Tasker and Dr. Randolph made these remarks in an accompanying editorial (JAMA. 2015;314:776-7. doi: 10.1001/jama.2015.9527).
The findings by Dr. Andersen and his associates provide fairly strong evidence that following current guidelines for epinephrine timing is best practice, supporting an AHA class I strength of recommendation.
The investigators are correct to note that observational data cannot establish causality. Almost all of these cardiac arrests were witnessed; approximately two-thirds occurred in the pediatric intensive care unit, operating room, or postanesthesia setting; and half of the patients were receiving mechanical ventilation. So it is possible that the link between timing of epinephrine and outcomes may simply reflect factors such as the circumstances of the cardiac arrest, the presence of an airway and intravenous access, or the quality of chest compressions.
Dr. Robert C. Tasker and Dr. Adriennne G. Randolph are with the division of critical care medicine, department of anesthesia, perioperative, and pain medicine at Boston Children’s Hospital and the department of anesthesia at Harvard Medical School. Dr. Tasker is also with the department of neurology at both institutions and Dr. Randolph is also with the department of pediatrics at Harvard. Both authors reported having no relevant financial conflicts of interest. Dr. Tasker and Dr. Randolph made these remarks in an accompanying editorial (JAMA. 2015;314:776-7. doi: 10.1001/jama.2015.9527).
Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published online Aug. 25 in JAMA.
For the approximately 16,000 U.S. children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.
It is highly unlikely that any such study will ever be done, given the ethical considerations, so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period, said Dr. Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, and the department of anesthesiology at Aarhus (Denmark) University and his associates.
All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.
Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (relative risk, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).
In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr. Andersen and his associates said (JAMA. 2015 Aug 25. doi: 10.1001/jama.2015.9678).
These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.
Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published online Aug. 25 in JAMA.
For the approximately 16,000 U.S. children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.
It is highly unlikely that any such study will ever be done, given the ethical considerations, so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period, said Dr. Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, and the department of anesthesiology at Aarhus (Denmark) University and his associates.
All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.
Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (relative risk, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).
In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr. Andersen and his associates said (JAMA. 2015 Aug 25. doi: 10.1001/jama.2015.9678).
These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.
FROM JAMA
Key clinical point: Delay in administering epinephrine was linked to poorer outcomes in pediatric in-hospital cardiac arrest.
Major finding: Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (RR, 0.95 per minute of delay).
Data source: A multicenter cohort study of 1,558 in-hospital cardiac arrests among pediatric patients across the United States during a 15-year period.
Disclosures: The National Heart, Lung, and Blood Institute and the American Heart Association supported the study. Dr. Andersen and his associates reported having no conflicts of interest.
Physical activity, omega-3 supplements didn’t improve cognitive outcomes
Neither a physical activity program nor omega-3 long-chain polyunsaturated fatty acid supplements improved cognitive function in two separate studies of high-risk elderly patients reported online Aug. 25 in JAMA.
Both studies were secondary analyses of large randomized clinical trials. Their findings contradict the results of many epidemiologic and observational studies attesting to the cognitive benefits of both lifestyle interventions.
The first study involved 1,635 sedentary men and women aged 70-89 years who had lower-extremity functional limitations and were participating in the LIFE (Lifestyle Interventions and Independence for Elders) trial at eight U.S. medical centers. These participants were randomly assigned to either a physical activity intervention (818 study subjects) or a health education program (817 control subjects) and were assessed with a comprehensive battery of neuropsychological tests every 6 months for 2 years, according to Dr. Kaycee M. Sink of the Sticht Center on Aging at Wake Forest University, Winston-Salem, N.C., and her associates.
The intervention comprised two weekly clinic visits plus three to four weekly home sessions focused on strength, flexibility, and balance training, as well as walking. The control situation consisted of weekly 60- to 90-minute workshops on topics such as travel safety, preventive services, legal and financial issues, and nutrition. As expected, the intervention group achieved a higher level of moderate to vigorous physical activity throughout follow-up (mean increase of 130.4 minutes/week), compared with the control group (mean increase of 30.5 minutes/week).
However, after 2 years, there were no significant differences between the two groups in either global cognitive scores or in individual scores on numerous measures of psychomotor speed, attention, concentration, working memory, word list learning, word recall, visuospatial function, figural memory, language, or executive function. There also were no differences in the rates of mild cognitive impairment, dementia, or both combined: 13.2% of the intervention group and 12.1% of the control group developed MCI or dementia by 2 years, a nonsignificant difference, the investigators said (JAMA. 2015;314[8]:781-90).
It is possible that the level of physical activity in this intervention may not have been sufficient to produce changes in cognitive measures, or that cognitive function improved in the short term but dissipated by the end of the second year of follow-up. Alternatively, the study population on the whole was well educated (more than two-thirds attended college), and high cognitive reserve may have protected against cognitive decline in both groups. It is also possible that the health education intervention provided enough cognitive and social stimulation to preserve cognitive function in the control group, Dr. Sink and her associates said.
The second report was an ancillary study of AREDS2 (Age-Related Eye Disease Study 2), a randomized clinical trial that assessed various dietary supplements’ effect on age-related macular degeneration and cataracts. This trial’s median 5-year follow-up of older patients (mean age, 73 years) gave researchers a chance to examine any possible cognitive benefits of treatment with omega-3 long-chain polyunsaturated fatty acids – docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and/or lutein/zeaxanthin, said Dr. Emily Y. Chew of the division of epidemiology and clinical applications at the National Eye Institute and National Institutes of Health, and her associates (JAMA 2015;314[8]:791-801).
The 3,073 study participants were assessed using eight tests of cognitive function after first “passing” a hearing handicap inventory, a depression scale, and the Telephone Interview of Cognitive Status to assure their functional status. The eight tests examined immediate and delayed recall, language, executive function, word fluency, memory, attention, and processing speed.
At 5-year follow-up, there were no significant differences between the two study groups in either a global assessment of cognitive function or in any of the individual component assessments. The yearly change in scores on the composite measure was –0.19 with supplements and –0.18 without supplements, a nonsignificant difference on their scale from –22 to +17, Dr. Chew and her associates said.
It is not yet known why abundant observational data support the use of these supplements to improve cognitive function but most randomized clinical trials, like this one, fail to show such beneficial effects. “It is possible that these supplements were started too late in the aging process” to exert an effect, or that a 5-year duration of treatment was insufficient, they noted.
These two high-quality, well-designed randomized clinical trials failed to demonstrate significant cognitive benefits with either physical activity or omega-3 supplements, but that shouldn’t lead to nihilism regarding lifestyle factors in older adults. There is abundant, clear evidence that both physical activity and a healthy diet improve a wide variety of health outcomes.
An active lifestyle throughout the lifespan would probably be more effective in preventing cognitive decline than [would] starting limited physical activity after the onset of aging. Similarly, adherence to a healthy diet throughout life would probably be more effective than initiating isolated nutritional supplements late in life.
Dr. Sudeep S. Gill is in the department of medicine and Dallas P. Seitz, Ph.D., is in the department of psychiatry at Queen’s University, Kingston (Ont.). Dr. Gill reported having no relevant financial disclosures and Dr. Seitz reported receiving an advisory board honorarium from Eli Lilly. Dr. Gill and Dr. Seitz made these remarks in an editorial accompanying the two reports on lifestyle interventions and cognitive health (JAMA 2015;314[8]:774-5).
These two high-quality, well-designed randomized clinical trials failed to demonstrate significant cognitive benefits with either physical activity or omega-3 supplements, but that shouldn’t lead to nihilism regarding lifestyle factors in older adults. There is abundant, clear evidence that both physical activity and a healthy diet improve a wide variety of health outcomes.
An active lifestyle throughout the lifespan would probably be more effective in preventing cognitive decline than [would] starting limited physical activity after the onset of aging. Similarly, adherence to a healthy diet throughout life would probably be more effective than initiating isolated nutritional supplements late in life.
Dr. Sudeep S. Gill is in the department of medicine and Dallas P. Seitz, Ph.D., is in the department of psychiatry at Queen’s University, Kingston (Ont.). Dr. Gill reported having no relevant financial disclosures and Dr. Seitz reported receiving an advisory board honorarium from Eli Lilly. Dr. Gill and Dr. Seitz made these remarks in an editorial accompanying the two reports on lifestyle interventions and cognitive health (JAMA 2015;314[8]:774-5).
These two high-quality, well-designed randomized clinical trials failed to demonstrate significant cognitive benefits with either physical activity or omega-3 supplements, but that shouldn’t lead to nihilism regarding lifestyle factors in older adults. There is abundant, clear evidence that both physical activity and a healthy diet improve a wide variety of health outcomes.
An active lifestyle throughout the lifespan would probably be more effective in preventing cognitive decline than [would] starting limited physical activity after the onset of aging. Similarly, adherence to a healthy diet throughout life would probably be more effective than initiating isolated nutritional supplements late in life.
Dr. Sudeep S. Gill is in the department of medicine and Dallas P. Seitz, Ph.D., is in the department of psychiatry at Queen’s University, Kingston (Ont.). Dr. Gill reported having no relevant financial disclosures and Dr. Seitz reported receiving an advisory board honorarium from Eli Lilly. Dr. Gill and Dr. Seitz made these remarks in an editorial accompanying the two reports on lifestyle interventions and cognitive health (JAMA 2015;314[8]:774-5).
Neither a physical activity program nor omega-3 long-chain polyunsaturated fatty acid supplements improved cognitive function in two separate studies of high-risk elderly patients reported online Aug. 25 in JAMA.
Both studies were secondary analyses of large randomized clinical trials. Their findings contradict the results of many epidemiologic and observational studies attesting to the cognitive benefits of both lifestyle interventions.
The first study involved 1,635 sedentary men and women aged 70-89 years who had lower-extremity functional limitations and were participating in the LIFE (Lifestyle Interventions and Independence for Elders) trial at eight U.S. medical centers. These participants were randomly assigned to either a physical activity intervention (818 study subjects) or a health education program (817 control subjects) and were assessed with a comprehensive battery of neuropsychological tests every 6 months for 2 years, according to Dr. Kaycee M. Sink of the Sticht Center on Aging at Wake Forest University, Winston-Salem, N.C., and her associates.
The intervention comprised two weekly clinic visits plus three to four weekly home sessions focused on strength, flexibility, and balance training, as well as walking. The control situation consisted of weekly 60- to 90-minute workshops on topics such as travel safety, preventive services, legal and financial issues, and nutrition. As expected, the intervention group achieved a higher level of moderate to vigorous physical activity throughout follow-up (mean increase of 130.4 minutes/week), compared with the control group (mean increase of 30.5 minutes/week).
However, after 2 years, there were no significant differences between the two groups in either global cognitive scores or in individual scores on numerous measures of psychomotor speed, attention, concentration, working memory, word list learning, word recall, visuospatial function, figural memory, language, or executive function. There also were no differences in the rates of mild cognitive impairment, dementia, or both combined: 13.2% of the intervention group and 12.1% of the control group developed MCI or dementia by 2 years, a nonsignificant difference, the investigators said (JAMA. 2015;314[8]:781-90).
It is possible that the level of physical activity in this intervention may not have been sufficient to produce changes in cognitive measures, or that cognitive function improved in the short term but dissipated by the end of the second year of follow-up. Alternatively, the study population on the whole was well educated (more than two-thirds attended college), and high cognitive reserve may have protected against cognitive decline in both groups. It is also possible that the health education intervention provided enough cognitive and social stimulation to preserve cognitive function in the control group, Dr. Sink and her associates said.
The second report was an ancillary study of AREDS2 (Age-Related Eye Disease Study 2), a randomized clinical trial that assessed various dietary supplements’ effect on age-related macular degeneration and cataracts. This trial’s median 5-year follow-up of older patients (mean age, 73 years) gave researchers a chance to examine any possible cognitive benefits of treatment with omega-3 long-chain polyunsaturated fatty acids – docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and/or lutein/zeaxanthin, said Dr. Emily Y. Chew of the division of epidemiology and clinical applications at the National Eye Institute and National Institutes of Health, and her associates (JAMA 2015;314[8]:791-801).
The 3,073 study participants were assessed using eight tests of cognitive function after first “passing” a hearing handicap inventory, a depression scale, and the Telephone Interview of Cognitive Status to assure their functional status. The eight tests examined immediate and delayed recall, language, executive function, word fluency, memory, attention, and processing speed.
At 5-year follow-up, there were no significant differences between the two study groups in either a global assessment of cognitive function or in any of the individual component assessments. The yearly change in scores on the composite measure was –0.19 with supplements and –0.18 without supplements, a nonsignificant difference on their scale from –22 to +17, Dr. Chew and her associates said.
It is not yet known why abundant observational data support the use of these supplements to improve cognitive function but most randomized clinical trials, like this one, fail to show such beneficial effects. “It is possible that these supplements were started too late in the aging process” to exert an effect, or that a 5-year duration of treatment was insufficient, they noted.
Neither a physical activity program nor omega-3 long-chain polyunsaturated fatty acid supplements improved cognitive function in two separate studies of high-risk elderly patients reported online Aug. 25 in JAMA.
Both studies were secondary analyses of large randomized clinical trials. Their findings contradict the results of many epidemiologic and observational studies attesting to the cognitive benefits of both lifestyle interventions.
The first study involved 1,635 sedentary men and women aged 70-89 years who had lower-extremity functional limitations and were participating in the LIFE (Lifestyle Interventions and Independence for Elders) trial at eight U.S. medical centers. These participants were randomly assigned to either a physical activity intervention (818 study subjects) or a health education program (817 control subjects) and were assessed with a comprehensive battery of neuropsychological tests every 6 months for 2 years, according to Dr. Kaycee M. Sink of the Sticht Center on Aging at Wake Forest University, Winston-Salem, N.C., and her associates.
The intervention comprised two weekly clinic visits plus three to four weekly home sessions focused on strength, flexibility, and balance training, as well as walking. The control situation consisted of weekly 60- to 90-minute workshops on topics such as travel safety, preventive services, legal and financial issues, and nutrition. As expected, the intervention group achieved a higher level of moderate to vigorous physical activity throughout follow-up (mean increase of 130.4 minutes/week), compared with the control group (mean increase of 30.5 minutes/week).
However, after 2 years, there were no significant differences between the two groups in either global cognitive scores or in individual scores on numerous measures of psychomotor speed, attention, concentration, working memory, word list learning, word recall, visuospatial function, figural memory, language, or executive function. There also were no differences in the rates of mild cognitive impairment, dementia, or both combined: 13.2% of the intervention group and 12.1% of the control group developed MCI or dementia by 2 years, a nonsignificant difference, the investigators said (JAMA. 2015;314[8]:781-90).
It is possible that the level of physical activity in this intervention may not have been sufficient to produce changes in cognitive measures, or that cognitive function improved in the short term but dissipated by the end of the second year of follow-up. Alternatively, the study population on the whole was well educated (more than two-thirds attended college), and high cognitive reserve may have protected against cognitive decline in both groups. It is also possible that the health education intervention provided enough cognitive and social stimulation to preserve cognitive function in the control group, Dr. Sink and her associates said.
The second report was an ancillary study of AREDS2 (Age-Related Eye Disease Study 2), a randomized clinical trial that assessed various dietary supplements’ effect on age-related macular degeneration and cataracts. This trial’s median 5-year follow-up of older patients (mean age, 73 years) gave researchers a chance to examine any possible cognitive benefits of treatment with omega-3 long-chain polyunsaturated fatty acids – docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and/or lutein/zeaxanthin, said Dr. Emily Y. Chew of the division of epidemiology and clinical applications at the National Eye Institute and National Institutes of Health, and her associates (JAMA 2015;314[8]:791-801).
The 3,073 study participants were assessed using eight tests of cognitive function after first “passing” a hearing handicap inventory, a depression scale, and the Telephone Interview of Cognitive Status to assure their functional status. The eight tests examined immediate and delayed recall, language, executive function, word fluency, memory, attention, and processing speed.
At 5-year follow-up, there were no significant differences between the two study groups in either a global assessment of cognitive function or in any of the individual component assessments. The yearly change in scores on the composite measure was –0.19 with supplements and –0.18 without supplements, a nonsignificant difference on their scale from –22 to +17, Dr. Chew and her associates said.
It is not yet known why abundant observational data support the use of these supplements to improve cognitive function but most randomized clinical trials, like this one, fail to show such beneficial effects. “It is possible that these supplements were started too late in the aging process” to exert an effect, or that a 5-year duration of treatment was insufficient, they noted.
FROM JAMA
Key clinical point: Neither physical activity nor omega-3 supplements improved cognitive function in two separate studies of high-risk elderly patients.
Major finding: There were no differences at 2 years in the rates of mild cognitive impairment, dementia, or both combined: 13.2% of the physical activity intervention group and 12.1% of the control group. In the supplements trial, yearly change in scores on the composite measure was –0.19 with omega-3 supplements and –0.18 without supplements, a nonsignificant difference on their scale from –22 to +17.
Data source: A secondary analysis of a randomized controlled clinical trial involving 1,635 elderly participants and assessing a physical activity intervention, and an ancillary study of a randomized clinical trial of dietary supplements in 3,073 elderly participants.
Disclosures: The LIFE study was supported by various institutes of the National Institutes of Health, Claude D. Pepper Older Americans Independence Centers, and the U.S. Department of Agriculture. Dr. Sink reported receiving a grant from Navidea, and her associates reported ties to the McKnight Brain Research Foundation, Baxter, Lilly, Grifols, Lundbeck, Regeneron, and Bay Cove Human Services. The AREDS ancillary study was supported by various institutes of the National Institutes of Health. Dr. Chew reported having no relevant financial disclosures, and one of her associates reported serving as a consultant for Kerman Health, Kalsec, DSM, and ScienceBased Health.
Mixed results for cancer survivorship care plan
A cancer survivorship care plan increased the information patients received yet failed to increase patient satisfaction with cancer care. Moreover, patients who received care plans experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those who did not, according to a study published online Aug. 24 in Journal of Clinical Oncology.
The Institute of Medicine and other groups recommend survivorship care plans (SCPs) for all cancer survivors to help them deal with the challenges they face after diagnosis. Yet few studies have examined SCPs’ effectiveness. To do so, researchers performed what they described as the first pragmatic, cluster-randomized longitudinal trial comparing an automatically generated SCP against usual care in routine clinical practice.
The study involved 221 women with newly diagnosed endometrial cancer treated at 12 medical centers in the Netherlands. Six of the hospitals were randomly assigned to provide usual care (102 patients) and six to provide SCPs (119 patients) immediately after initial surgery, with updated SCPs offered 6 and 12 months later, said Kim A. H. Nicolaije of Tilburg University and the Comprehensive Cancer Center the Netherlands, Eindhoven, and her associates.
Usual care included verbal and written information about diagnosis and treatment, the recovery period, signs of recurrence, and hospital contacts; no additional information was given during follow-up, except for referrals when indicated.
The SCP entailed a treatment summary tailored to each patient’s diagnostic test results, tumor stage and grade, comorbidities, and evolving complications. It addressed possible short- and long-term effects of the cancer and its treatments on physical, social, and sexual life; signs of recurrence and secondary tumors; services such as rehabilitation, psychosocial support, and supportive care; and contact information for hospital personnel and outside specialists.
At follow-up, participants in the SCP group said they’d received more information about their disease, its treatments, other services available to them, different places where they could seek care, and ways they could help themselves get well, compared with the usual-care group. Yet there were no significant differences between the two study groups in several measures of satisfaction with the information provided or with the care itself. Furthermore, patients in the SCP group said they experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those in the usual-care group.
The SCPs called for including patients’ primary care physicians in the plans while usual care did not, and patients in the SCP group reported having more cancer-related contact with their primary-care physicians than those in the usual-care group. Yet this increased contact did not lead to better patient satisfaction, Ms. Nicolaije and her associates said (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2014.60.3399).
It is unclear whether these effects are harmful or beneficial for patients. “One could argue that receiving an SCP raises patients’ awareness of cancer-related symptoms and empowers them to find the necessary support,” even if they don’t recognize this as a benefit, the investigators added.
The Dutch Cancer Society supported the study. Ms. Nicolaije reported having no conflicts of interest; a coauthor reported receiving research funding and reimbursement for expenses from Janssen Pharmaceuticals.
Survivorship care plans have been recommended for the past decade, but their implementation has been slow, low, and sporadic. And we still don’t have a clear answer as to their effectiveness.
The medical community should recognize that null or negative results on SCP effectiveness, such as those reported by Nicolaije et al., may not reflect some inherent defect of SCPs but rather the poor or inconsistent implementation of an SCP. Fully 26% of the patients in the SCP group in this trial reported that they had never in fact received an SCP.
In addition, being better informed about late or long-term effects of cancer or its treatment may well give rise to “increased concerns” and feeling “more emotionally affected” in the year following diagnosis, but may also yield great benefits later on – a possibility that wasn’t addressed in this trial.
Deborah K. Mayer, Ph.D., is at the University of North Carolina School of Nursing and Lineberger Comprehensive Cancer Center, both in Chapel Hill. She reported having no conflicts of interest; one of her associates reported serving as a consultant to Medivation/Astellas Pharma and receiving research funding from Accuray. Dr. Mayer and her associates made these remarks in an editorial accompanying Ms. Nicolaije’s report (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2015.62.6937).
Survivorship care plans have been recommended for the past decade, but their implementation has been slow, low, and sporadic. And we still don’t have a clear answer as to their effectiveness.
The medical community should recognize that null or negative results on SCP effectiveness, such as those reported by Nicolaije et al., may not reflect some inherent defect of SCPs but rather the poor or inconsistent implementation of an SCP. Fully 26% of the patients in the SCP group in this trial reported that they had never in fact received an SCP.
In addition, being better informed about late or long-term effects of cancer or its treatment may well give rise to “increased concerns” and feeling “more emotionally affected” in the year following diagnosis, but may also yield great benefits later on – a possibility that wasn’t addressed in this trial.
Deborah K. Mayer, Ph.D., is at the University of North Carolina School of Nursing and Lineberger Comprehensive Cancer Center, both in Chapel Hill. She reported having no conflicts of interest; one of her associates reported serving as a consultant to Medivation/Astellas Pharma and receiving research funding from Accuray. Dr. Mayer and her associates made these remarks in an editorial accompanying Ms. Nicolaije’s report (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2015.62.6937).
Survivorship care plans have been recommended for the past decade, but their implementation has been slow, low, and sporadic. And we still don’t have a clear answer as to their effectiveness.
The medical community should recognize that null or negative results on SCP effectiveness, such as those reported by Nicolaije et al., may not reflect some inherent defect of SCPs but rather the poor or inconsistent implementation of an SCP. Fully 26% of the patients in the SCP group in this trial reported that they had never in fact received an SCP.
In addition, being better informed about late or long-term effects of cancer or its treatment may well give rise to “increased concerns” and feeling “more emotionally affected” in the year following diagnosis, but may also yield great benefits later on – a possibility that wasn’t addressed in this trial.
Deborah K. Mayer, Ph.D., is at the University of North Carolina School of Nursing and Lineberger Comprehensive Cancer Center, both in Chapel Hill. She reported having no conflicts of interest; one of her associates reported serving as a consultant to Medivation/Astellas Pharma and receiving research funding from Accuray. Dr. Mayer and her associates made these remarks in an editorial accompanying Ms. Nicolaije’s report (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2015.62.6937).
A cancer survivorship care plan increased the information patients received yet failed to increase patient satisfaction with cancer care. Moreover, patients who received care plans experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those who did not, according to a study published online Aug. 24 in Journal of Clinical Oncology.
The Institute of Medicine and other groups recommend survivorship care plans (SCPs) for all cancer survivors to help them deal with the challenges they face after diagnosis. Yet few studies have examined SCPs’ effectiveness. To do so, researchers performed what they described as the first pragmatic, cluster-randomized longitudinal trial comparing an automatically generated SCP against usual care in routine clinical practice.
The study involved 221 women with newly diagnosed endometrial cancer treated at 12 medical centers in the Netherlands. Six of the hospitals were randomly assigned to provide usual care (102 patients) and six to provide SCPs (119 patients) immediately after initial surgery, with updated SCPs offered 6 and 12 months later, said Kim A. H. Nicolaije of Tilburg University and the Comprehensive Cancer Center the Netherlands, Eindhoven, and her associates.
Usual care included verbal and written information about diagnosis and treatment, the recovery period, signs of recurrence, and hospital contacts; no additional information was given during follow-up, except for referrals when indicated.
The SCP entailed a treatment summary tailored to each patient’s diagnostic test results, tumor stage and grade, comorbidities, and evolving complications. It addressed possible short- and long-term effects of the cancer and its treatments on physical, social, and sexual life; signs of recurrence and secondary tumors; services such as rehabilitation, psychosocial support, and supportive care; and contact information for hospital personnel and outside specialists.
At follow-up, participants in the SCP group said they’d received more information about their disease, its treatments, other services available to them, different places where they could seek care, and ways they could help themselves get well, compared with the usual-care group. Yet there were no significant differences between the two study groups in several measures of satisfaction with the information provided or with the care itself. Furthermore, patients in the SCP group said they experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those in the usual-care group.
The SCPs called for including patients’ primary care physicians in the plans while usual care did not, and patients in the SCP group reported having more cancer-related contact with their primary-care physicians than those in the usual-care group. Yet this increased contact did not lead to better patient satisfaction, Ms. Nicolaije and her associates said (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2014.60.3399).
It is unclear whether these effects are harmful or beneficial for patients. “One could argue that receiving an SCP raises patients’ awareness of cancer-related symptoms and empowers them to find the necessary support,” even if they don’t recognize this as a benefit, the investigators added.
The Dutch Cancer Society supported the study. Ms. Nicolaije reported having no conflicts of interest; a coauthor reported receiving research funding and reimbursement for expenses from Janssen Pharmaceuticals.
A cancer survivorship care plan increased the information patients received yet failed to increase patient satisfaction with cancer care. Moreover, patients who received care plans experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those who did not, according to a study published online Aug. 24 in Journal of Clinical Oncology.
The Institute of Medicine and other groups recommend survivorship care plans (SCPs) for all cancer survivors to help them deal with the challenges they face after diagnosis. Yet few studies have examined SCPs’ effectiveness. To do so, researchers performed what they described as the first pragmatic, cluster-randomized longitudinal trial comparing an automatically generated SCP against usual care in routine clinical practice.
The study involved 221 women with newly diagnosed endometrial cancer treated at 12 medical centers in the Netherlands. Six of the hospitals were randomly assigned to provide usual care (102 patients) and six to provide SCPs (119 patients) immediately after initial surgery, with updated SCPs offered 6 and 12 months later, said Kim A. H. Nicolaije of Tilburg University and the Comprehensive Cancer Center the Netherlands, Eindhoven, and her associates.
Usual care included verbal and written information about diagnosis and treatment, the recovery period, signs of recurrence, and hospital contacts; no additional information was given during follow-up, except for referrals when indicated.
The SCP entailed a treatment summary tailored to each patient’s diagnostic test results, tumor stage and grade, comorbidities, and evolving complications. It addressed possible short- and long-term effects of the cancer and its treatments on physical, social, and sexual life; signs of recurrence and secondary tumors; services such as rehabilitation, psychosocial support, and supportive care; and contact information for hospital personnel and outside specialists.
At follow-up, participants in the SCP group said they’d received more information about their disease, its treatments, other services available to them, different places where they could seek care, and ways they could help themselves get well, compared with the usual-care group. Yet there were no significant differences between the two study groups in several measures of satisfaction with the information provided or with the care itself. Furthermore, patients in the SCP group said they experienced more symptoms, were more concerned about their illness, and were more affected emotionally than were those in the usual-care group.
The SCPs called for including patients’ primary care physicians in the plans while usual care did not, and patients in the SCP group reported having more cancer-related contact with their primary-care physicians than those in the usual-care group. Yet this increased contact did not lead to better patient satisfaction, Ms. Nicolaije and her associates said (J Clin Oncol 2015 Aug 24. doi:10.1200/JCO.2014.60.3399).
It is unclear whether these effects are harmful or beneficial for patients. “One could argue that receiving an SCP raises patients’ awareness of cancer-related symptoms and empowers them to find the necessary support,” even if they don’t recognize this as a benefit, the investigators added.
The Dutch Cancer Society supported the study. Ms. Nicolaije reported having no conflicts of interest; a coauthor reported receiving research funding and reimbursement for expenses from Janssen Pharmaceuticals.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: A cancer survivorship care plan did not improve endometrial cancer patients’ satisfaction with information provision or with health care.
Major finding: Participants in the SCP group said they had received more information about their disease, its treatments, other services available to them, and ways they could help themselves get well, compared with the usual-care group, but they did not report more satisfaction with the information or with their cancer care.
Data source: A longitudinal, cluster-randomized trial of 221 women with newly diagnosed endometrial cancer treated at 12 hospitals in the Netherlands and followed for 1 year.
Disclosures: The Dutch Cancer Society supported the study. Ms. Nicolaije reported having no conflicts of interest; a coauthor reported receiving research funding and reimbursement for expenses from Janssen Pharmaceuticals.
Adding trebananib increased toxicity for metastatic RCC patients
Adding trebananib to sunitinib increased treatment toxicity but also appeared to enhance antitumor activity in an international phase II study involving 85 adults with metastatic renal-cell carcinoma, investigators reported online Aug. 24 in the Journal of Clinical Oncology.
Trebananib is an investigational recombinant protein that has a different pathway of anti–vascular endothelial growth factor (VEGF) activity than does sunitinib. Researchers hoped that combining the two agents would forestall the resistance to VEGF pathway blockade that typically develops within 8-12 months of beginning monotherapy. Most VEGF blockers, however, produce significant toxicity when combined. To examine the toxicity of the combination of trebananib and sunitinib, investigators conducted this open-label study at 18 sites in the United States, Europe, and Australia.
One cohort (43 patients) received 10 mg/kg intravenous trebananib once weekly plus oral sunitinib in a standard regimen; a second cohort (42 patients) received 15 mg/kg intravenous trebananib once weekly plus oral sunitinib. Treatment continued until disease progressed, unacceptable toxic effects developed, or participants withdrew consent, said Dr. Michael B. Atkins of Georgetown University Lombardi Comprehensive Cancer Center, Washington, D.C., and his associates.
The primary endpoint was treatment toxicity as measured by the incidence of adverse events, dose interruptions of sunitinib, or significant laboratory abnormalities. Grade 3 or higher treatment-related adverse events developed in 58% of the first cohort and 69% of the second cohort and included one case of fatal pulmonary edema considered possibly related to trebananib. Dose interruptions of sunitinib due to adverse events or laboratory abnormalities occurred in 70% of the first cohort and 86% of the second cohort. Other noteworthy adverse events included edema, which affected approximately 70% of both cohorts; pleural effusion; ascites; one GI perforation; one myocardial infarction; and two serious venous thromboembolisms, the investigators reported.
This represents a significant increase in toxicity for the combined therapy, compared with sunitinib monotherapy, Dr. Atkins and his associates said (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.60.6012).
They noted, however, that 66% of the first cohort and 74% of the second cohort were able to continue full doses of the combined therapy despite frequent dose interruptions, and that 80% of the first cohort and 88% of the second cohort showed reductions in tumor burden. Median progression-free survival was 13.9 months and 16.3 months, respectively, which compares favorably to the median 8-11 month PFS reported in the literature for sunitinib monotherapy. Similarly, the overall response rate was 58% and 63%, respectively, which also bests the overall response rate reported in the literature.
Thus, the combination therapy may enhance antitumor activity and improve survival outcomes in larger phase III studies that focus on treatment efficacy rather than toxicity, Dr. Atkins and his associates said.
This study was supported by Amgen. Dr. Atkins reported serving as a consultant for Amgen, Merck, Genentech, Pfizer, Novartis, cCAM Biotherapeutics, X4 Pharmaceuticals, NeoStem, Eli Lilly, Alkermes, Infinity, and Bristol-Myers Squibb and receiving honoraria from Bristol-Myers Squibb. His associates reported ties to numerous industry sources.
Adding trebananib to sunitinib increased treatment toxicity but also appeared to enhance antitumor activity in an international phase II study involving 85 adults with metastatic renal-cell carcinoma, investigators reported online Aug. 24 in the Journal of Clinical Oncology.
Trebananib is an investigational recombinant protein that has a different pathway of anti–vascular endothelial growth factor (VEGF) activity than does sunitinib. Researchers hoped that combining the two agents would forestall the resistance to VEGF pathway blockade that typically develops within 8-12 months of beginning monotherapy. Most VEGF blockers, however, produce significant toxicity when combined. To examine the toxicity of the combination of trebananib and sunitinib, investigators conducted this open-label study at 18 sites in the United States, Europe, and Australia.
One cohort (43 patients) received 10 mg/kg intravenous trebananib once weekly plus oral sunitinib in a standard regimen; a second cohort (42 patients) received 15 mg/kg intravenous trebananib once weekly plus oral sunitinib. Treatment continued until disease progressed, unacceptable toxic effects developed, or participants withdrew consent, said Dr. Michael B. Atkins of Georgetown University Lombardi Comprehensive Cancer Center, Washington, D.C., and his associates.
The primary endpoint was treatment toxicity as measured by the incidence of adverse events, dose interruptions of sunitinib, or significant laboratory abnormalities. Grade 3 or higher treatment-related adverse events developed in 58% of the first cohort and 69% of the second cohort and included one case of fatal pulmonary edema considered possibly related to trebananib. Dose interruptions of sunitinib due to adverse events or laboratory abnormalities occurred in 70% of the first cohort and 86% of the second cohort. Other noteworthy adverse events included edema, which affected approximately 70% of both cohorts; pleural effusion; ascites; one GI perforation; one myocardial infarction; and two serious venous thromboembolisms, the investigators reported.
This represents a significant increase in toxicity for the combined therapy, compared with sunitinib monotherapy, Dr. Atkins and his associates said (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.60.6012).
They noted, however, that 66% of the first cohort and 74% of the second cohort were able to continue full doses of the combined therapy despite frequent dose interruptions, and that 80% of the first cohort and 88% of the second cohort showed reductions in tumor burden. Median progression-free survival was 13.9 months and 16.3 months, respectively, which compares favorably to the median 8-11 month PFS reported in the literature for sunitinib monotherapy. Similarly, the overall response rate was 58% and 63%, respectively, which also bests the overall response rate reported in the literature.
Thus, the combination therapy may enhance antitumor activity and improve survival outcomes in larger phase III studies that focus on treatment efficacy rather than toxicity, Dr. Atkins and his associates said.
This study was supported by Amgen. Dr. Atkins reported serving as a consultant for Amgen, Merck, Genentech, Pfizer, Novartis, cCAM Biotherapeutics, X4 Pharmaceuticals, NeoStem, Eli Lilly, Alkermes, Infinity, and Bristol-Myers Squibb and receiving honoraria from Bristol-Myers Squibb. His associates reported ties to numerous industry sources.
Adding trebananib to sunitinib increased treatment toxicity but also appeared to enhance antitumor activity in an international phase II study involving 85 adults with metastatic renal-cell carcinoma, investigators reported online Aug. 24 in the Journal of Clinical Oncology.
Trebananib is an investigational recombinant protein that has a different pathway of anti–vascular endothelial growth factor (VEGF) activity than does sunitinib. Researchers hoped that combining the two agents would forestall the resistance to VEGF pathway blockade that typically develops within 8-12 months of beginning monotherapy. Most VEGF blockers, however, produce significant toxicity when combined. To examine the toxicity of the combination of trebananib and sunitinib, investigators conducted this open-label study at 18 sites in the United States, Europe, and Australia.
One cohort (43 patients) received 10 mg/kg intravenous trebananib once weekly plus oral sunitinib in a standard regimen; a second cohort (42 patients) received 15 mg/kg intravenous trebananib once weekly plus oral sunitinib. Treatment continued until disease progressed, unacceptable toxic effects developed, or participants withdrew consent, said Dr. Michael B. Atkins of Georgetown University Lombardi Comprehensive Cancer Center, Washington, D.C., and his associates.
The primary endpoint was treatment toxicity as measured by the incidence of adverse events, dose interruptions of sunitinib, or significant laboratory abnormalities. Grade 3 or higher treatment-related adverse events developed in 58% of the first cohort and 69% of the second cohort and included one case of fatal pulmonary edema considered possibly related to trebananib. Dose interruptions of sunitinib due to adverse events or laboratory abnormalities occurred in 70% of the first cohort and 86% of the second cohort. Other noteworthy adverse events included edema, which affected approximately 70% of both cohorts; pleural effusion; ascites; one GI perforation; one myocardial infarction; and two serious venous thromboembolisms, the investigators reported.
This represents a significant increase in toxicity for the combined therapy, compared with sunitinib monotherapy, Dr. Atkins and his associates said (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.60.6012).
They noted, however, that 66% of the first cohort and 74% of the second cohort were able to continue full doses of the combined therapy despite frequent dose interruptions, and that 80% of the first cohort and 88% of the second cohort showed reductions in tumor burden. Median progression-free survival was 13.9 months and 16.3 months, respectively, which compares favorably to the median 8-11 month PFS reported in the literature for sunitinib monotherapy. Similarly, the overall response rate was 58% and 63%, respectively, which also bests the overall response rate reported in the literature.
Thus, the combination therapy may enhance antitumor activity and improve survival outcomes in larger phase III studies that focus on treatment efficacy rather than toxicity, Dr. Atkins and his associates said.
This study was supported by Amgen. Dr. Atkins reported serving as a consultant for Amgen, Merck, Genentech, Pfizer, Novartis, cCAM Biotherapeutics, X4 Pharmaceuticals, NeoStem, Eli Lilly, Alkermes, Infinity, and Bristol-Myers Squibb and receiving honoraria from Bristol-Myers Squibb. His associates reported ties to numerous industry sources.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Adding trebananib to sunitinib increased toxicity but may enhance antitumor activity in metastatic renal-cell cancer.
Major finding: Adverse events developed in 58% of the first cohort and 69% of the second cohort, and dose interruptions occurred in 70% of the first cohort and 86% of the second cohort.
Data source: An international, open-label, phase II uncontrolled clinical trial involving 85 patients with metastatic renal-cell cancer.
Disclosures: This study was supported by Amgen. Dr. Atkins reported serving as a consultant for Amgen, Merck, Genentech, Pfizer, Novartis, cCAM Biotherapeutics, X4 Pharmaceuticals, NeoStem, Eli Lilly, Alkermes, Infinity, and Bristol-Myers Squibb and receiving honoraria from Bristol-Myers Squibb. His associates reported ties to numerous industry sources.
ACOG Recommends Against First-trimester Preeclampsia Tests
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
FROM OBSTETRICS & GYNECOLOGY
Vemurafenib looks promising for several nonmelanoma malignancies
Vemurafenib showed promising activity against several nonmelanoma cancers carrying BRAF V600 mutations in a preliminary phase II study reported online Aug. 20 in the New England Journal of Medicine.
Vemurafenib, a selective oral inhibitor of the BRAF V600 kinase, has produced a 50% response rate and improved survival in patients with metastatic melanoma expressing BRAF V600 mutations. Researchers subsequently identified the same mutations in numerous other tumor types, many of which are aggressive and some of which have no effective treatment. But the drug’s efficacy against these malignancies has not been examined systematically until now, because of “the large number of tumor types involved, the low frequency of BRAF V600 mutations, and the rarity of some of the cancers,” said Dr. David M. Hyman of Memorial Sloan Kettering Cancer Center, New York, and his associates.
To perform such an exploratory investigation, Dr. Hyman and his colleagues used a “basket” study design allowing enrollment of 122 patients from 23 medical centers worldwide who had advanced BRAF-V600–positive non–small cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, multiple myeloma, Erdheim-Chester disease, Langerhans-cell histiocytosis, anaplastic thyroid cancer, or “other” malignancies. A total of 95 of these participants received vemurafenib monotherapy, and 27 who had colorectal cancer received vemurafenib plus cetuximab combination therapy.
After 8 weeks of treatment, many patients showed partial or complete responses. Continued treatment often yielded tumor regression and prolonged stabilization of disease. The agent was particularly effective against non–small cell lung cancer, with an objective response rate of 42% among 19 evaluable patients, and against Erdheim-Chester disease and Langerhans-cell histiocytosis, with an objective response rate of 43% among 14 evaluable patients. The latter two malignancies are closely related orphan diseases with no approved therapies; none of these patients showed disease progression while taking vemurafenib, Dr. Hyman and his associates said (New Engl. J. Med. 2015 Aug 20 [doi:10.1056/NEJMoa1502309]).
Vemurafenib also showed modest but promising activity against anaplastic thyroid cancer, cholangiocarcinoma, anaplastic pleomorphic xanthoastrocytoma, salivary-duct cancer, clear-cell sarcoma, low-grade serous ovarian cancer, high-grade glioblastoma, anaplastic ependymoma, pancreatic cancer, and carcinoma of unknown primary type. Most of these cancers have limited therapeutic options. However, these results must be interpreted with caution because the largest of these subgroups of patients only comprised 8 patients.
Vemurafenib showed promising activity against several nonmelanoma cancers carrying BRAF V600 mutations in a preliminary phase II study reported online Aug. 20 in the New England Journal of Medicine.
Vemurafenib, a selective oral inhibitor of the BRAF V600 kinase, has produced a 50% response rate and improved survival in patients with metastatic melanoma expressing BRAF V600 mutations. Researchers subsequently identified the same mutations in numerous other tumor types, many of which are aggressive and some of which have no effective treatment. But the drug’s efficacy against these malignancies has not been examined systematically until now, because of “the large number of tumor types involved, the low frequency of BRAF V600 mutations, and the rarity of some of the cancers,” said Dr. David M. Hyman of Memorial Sloan Kettering Cancer Center, New York, and his associates.
To perform such an exploratory investigation, Dr. Hyman and his colleagues used a “basket” study design allowing enrollment of 122 patients from 23 medical centers worldwide who had advanced BRAF-V600–positive non–small cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, multiple myeloma, Erdheim-Chester disease, Langerhans-cell histiocytosis, anaplastic thyroid cancer, or “other” malignancies. A total of 95 of these participants received vemurafenib monotherapy, and 27 who had colorectal cancer received vemurafenib plus cetuximab combination therapy.
After 8 weeks of treatment, many patients showed partial or complete responses. Continued treatment often yielded tumor regression and prolonged stabilization of disease. The agent was particularly effective against non–small cell lung cancer, with an objective response rate of 42% among 19 evaluable patients, and against Erdheim-Chester disease and Langerhans-cell histiocytosis, with an objective response rate of 43% among 14 evaluable patients. The latter two malignancies are closely related orphan diseases with no approved therapies; none of these patients showed disease progression while taking vemurafenib, Dr. Hyman and his associates said (New Engl. J. Med. 2015 Aug 20 [doi:10.1056/NEJMoa1502309]).
Vemurafenib also showed modest but promising activity against anaplastic thyroid cancer, cholangiocarcinoma, anaplastic pleomorphic xanthoastrocytoma, salivary-duct cancer, clear-cell sarcoma, low-grade serous ovarian cancer, high-grade glioblastoma, anaplastic ependymoma, pancreatic cancer, and carcinoma of unknown primary type. Most of these cancers have limited therapeutic options. However, these results must be interpreted with caution because the largest of these subgroups of patients only comprised 8 patients.
Vemurafenib showed promising activity against several nonmelanoma cancers carrying BRAF V600 mutations in a preliminary phase II study reported online Aug. 20 in the New England Journal of Medicine.
Vemurafenib, a selective oral inhibitor of the BRAF V600 kinase, has produced a 50% response rate and improved survival in patients with metastatic melanoma expressing BRAF V600 mutations. Researchers subsequently identified the same mutations in numerous other tumor types, many of which are aggressive and some of which have no effective treatment. But the drug’s efficacy against these malignancies has not been examined systematically until now, because of “the large number of tumor types involved, the low frequency of BRAF V600 mutations, and the rarity of some of the cancers,” said Dr. David M. Hyman of Memorial Sloan Kettering Cancer Center, New York, and his associates.
To perform such an exploratory investigation, Dr. Hyman and his colleagues used a “basket” study design allowing enrollment of 122 patients from 23 medical centers worldwide who had advanced BRAF-V600–positive non–small cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, breast cancer, multiple myeloma, Erdheim-Chester disease, Langerhans-cell histiocytosis, anaplastic thyroid cancer, or “other” malignancies. A total of 95 of these participants received vemurafenib monotherapy, and 27 who had colorectal cancer received vemurafenib plus cetuximab combination therapy.
After 8 weeks of treatment, many patients showed partial or complete responses. Continued treatment often yielded tumor regression and prolonged stabilization of disease. The agent was particularly effective against non–small cell lung cancer, with an objective response rate of 42% among 19 evaluable patients, and against Erdheim-Chester disease and Langerhans-cell histiocytosis, with an objective response rate of 43% among 14 evaluable patients. The latter two malignancies are closely related orphan diseases with no approved therapies; none of these patients showed disease progression while taking vemurafenib, Dr. Hyman and his associates said (New Engl. J. Med. 2015 Aug 20 [doi:10.1056/NEJMoa1502309]).
Vemurafenib also showed modest but promising activity against anaplastic thyroid cancer, cholangiocarcinoma, anaplastic pleomorphic xanthoastrocytoma, salivary-duct cancer, clear-cell sarcoma, low-grade serous ovarian cancer, high-grade glioblastoma, anaplastic ependymoma, pancreatic cancer, and carcinoma of unknown primary type. Most of these cancers have limited therapeutic options. However, these results must be interpreted with caution because the largest of these subgroups of patients only comprised 8 patients.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Vemurafenib shows promising activity against several nonmelanoma cancers with BRAF V600 mutations, including non–small cell lung cancer (NSCLC).
Major finding: Vemurafenib was particularly effective against NSCLC, with an objective response rate of 42% among 19 evaluable patients, and against Erdheim-Chester disease and Langerhans-cell histiocytosis, with an objective response rate of 43% among 14 evaluable patients.
Data source: A preliminary phase II “basket” study to identify signals of activity against several tumor types expressing BRAF V600 mutations in 122 patients at 23 medical centers worldwide.
Disclosures: This study was supported by F. Hoffmann-La Roche/Genentech. Dr. Hyman reported receiving personal fees from Chugai and Santa Maria Biotherapeutics and nonfinancial support from PUMA. He also reported a pending patent related to detecting and monitoring genetic mutations in histiocytosis. His associates reported ties to numerous industry sources.
ACOG recommends against first-trimester preeclampsia tests
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
Commercial screening tests that purport to predict early-onset preeclampsia may do more harm than good and are not recommended, according to the American College of Obstetricians and Gynecologists.
Early-onset preeclampsia does signal great risk for both mother and infant, and early identification of pregnancies at high risk “would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease.” But the effectiveness of this approach is undercut by the low positive predictive value of currently available tests, according to a new policy statement from ACOG’s Committee on Obstetric Practice published Aug. 19 (Obstet Gynecol 2015;126:e25-7.).
“These tests require a large number of women to be identified as high risk and to potentially undergo intensive surveillance in order to detect one case of early-onset preeclampsia,” the committee members wrote.
Moreover, there are no data showing that using these screening tests improve clinical outcomes.
Taking a detailed medical history to assess risk factors remains “the best and only recommended screening approach for preeclampsia,” according to ACOG. The medical history should remain the screening method of choice until high-quality evidence demonstrates that aspirin and other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests, ACOG recommended.
“For a first-trimester risk assessment for preeclampsia to be useful in clinical practice, future screening tests will need to have sensitivities and [positive predictive values] high enough to accurately identify women who will develop preeclampsia, and interventions will need to be available that improve clinical outcome in women who test positive,” the committee members wrote.
The new committee opinion has been endorsed by the Society for Maternal-Fetal Medicine.
FROM OBSTETRICS & GYNECOLOGY
E-cigarettes precede tobacco smoking in ninth-graders
Ninth-graders who have used electronic cigarettes are much more likely than are nonusers to try regular cigarettes, cigars, and hookahs during the subsequent year, according to a report published online Aug. 18 in JAMA.
E-cigarettes are handheld battery-operated devices that heat a liquid composed of nicotine, propylene glycol or glycerin, flavorings, and other chemicals to create a vapor that is inhaled, simulating the experience of cigarette smoking. Their main potential benefit is to help adult smokers switch from using the more unhealthy combustible tobacco.
However, critics argue that adolescents who use e-cigarettes may be more likely to try other products that deliver nicotine, which would perpetuate the current epidemic of tobacco-related illness, said Adam M. Leventhal, Ph.D., of the department of preventive medicine, University of Southern California, Los Angeles, and his associates.
The investigators analyzed data from a longitudinal survey of substance use and mental health among high school students. In their prospective observational study, they focused on 2,530 demographically diverse students in ninth grade at 10 Los Angeles–area public high schools. The students were nonsmokers at baseline. A total of 222 of these adolescents reported that they had used e-cigarettes, while 2,308 had not.
Adolescents who had used e-cigarettes were much more likely than were nonusers to report trying combustible tobacco products during the next 6 months (30.7% vs 8.1%) and during the next 12 months (25.2% vs 9.3%), for an odds ratio of 4.27 averaged across the two study periods. This association was strong for each of the combustible tobacco products assessed, with an OR of 2.65 for regular cigarettes, an OR of 4.85 for full-size cigars or cigarillos, and an OR of 3.25 for hookahs.
When the data were adjusted to account for many sociodemographic, environmental, and intrapersonal characteristics known to influence smoking, the ORs declined but the associations remained strong and statistically significant, ranging from 1.75 to 2.96, depending on the smoking product, Dr. Leventhal and his associates said (JAMA. 2015;314[7]:700-707). One possible explanation for these findings is that adolescents who used e-cigarettes enjoyed the experience and were more likely to experiment with other nicotine-containing products. However, “because this is an observational study, and one of the first to address this issue, inferences regarding whether this association is or is not causal cannot yet be made,” they noted.
The study by Leventhal et al. presents the “strongest evidence to date” that e-cigarettes may pose a health hazard by encouraging adolescents to start smoking conventional tobacco products.
But regardless of whether e-cigarettes are a “gateway” drug, there is no reason for adolescents to use a product for which the purported intent is to help adults quit smoking. To protect youths, the same sales, marketing, and use restrictions that apply to combustible cigarettes should – promptly and effectively – be applied to e-cigarettes.
The Food and Drug Administration should set a minimum age of sale, require health warnings on e-cigarettes, and consider regulatory activities such as banning e-cigarette flavorings and prohibiting advertising in youth-oriented media. And states and communities should restrict e-cigarette smoking in public places and workplaces to avoid normalizing the behavior.
Nancy A. Rigotti, M.D., is in the department of medicine at Massachusetts General Hospital and Harvard Medical School, Boston. She reported receiving grants and nonfinancial support from Pfizer, and nonfinancial support from Arena Pharmaceuticals. Dr. Rigotti made these remarks in an editorial accompanying Dr. Leventhal’s report (JAMA 2015;314[7]:673-4).
The study by Leventhal et al. presents the “strongest evidence to date” that e-cigarettes may pose a health hazard by encouraging adolescents to start smoking conventional tobacco products.
But regardless of whether e-cigarettes are a “gateway” drug, there is no reason for adolescents to use a product for which the purported intent is to help adults quit smoking. To protect youths, the same sales, marketing, and use restrictions that apply to combustible cigarettes should – promptly and effectively – be applied to e-cigarettes.
The Food and Drug Administration should set a minimum age of sale, require health warnings on e-cigarettes, and consider regulatory activities such as banning e-cigarette flavorings and prohibiting advertising in youth-oriented media. And states and communities should restrict e-cigarette smoking in public places and workplaces to avoid normalizing the behavior.
Nancy A. Rigotti, M.D., is in the department of medicine at Massachusetts General Hospital and Harvard Medical School, Boston. She reported receiving grants and nonfinancial support from Pfizer, and nonfinancial support from Arena Pharmaceuticals. Dr. Rigotti made these remarks in an editorial accompanying Dr. Leventhal’s report (JAMA 2015;314[7]:673-4).
The study by Leventhal et al. presents the “strongest evidence to date” that e-cigarettes may pose a health hazard by encouraging adolescents to start smoking conventional tobacco products.
But regardless of whether e-cigarettes are a “gateway” drug, there is no reason for adolescents to use a product for which the purported intent is to help adults quit smoking. To protect youths, the same sales, marketing, and use restrictions that apply to combustible cigarettes should – promptly and effectively – be applied to e-cigarettes.
The Food and Drug Administration should set a minimum age of sale, require health warnings on e-cigarettes, and consider regulatory activities such as banning e-cigarette flavorings and prohibiting advertising in youth-oriented media. And states and communities should restrict e-cigarette smoking in public places and workplaces to avoid normalizing the behavior.
Nancy A. Rigotti, M.D., is in the department of medicine at Massachusetts General Hospital and Harvard Medical School, Boston. She reported receiving grants and nonfinancial support from Pfizer, and nonfinancial support from Arena Pharmaceuticals. Dr. Rigotti made these remarks in an editorial accompanying Dr. Leventhal’s report (JAMA 2015;314[7]:673-4).
Ninth-graders who have used electronic cigarettes are much more likely than are nonusers to try regular cigarettes, cigars, and hookahs during the subsequent year, according to a report published online Aug. 18 in JAMA.
E-cigarettes are handheld battery-operated devices that heat a liquid composed of nicotine, propylene glycol or glycerin, flavorings, and other chemicals to create a vapor that is inhaled, simulating the experience of cigarette smoking. Their main potential benefit is to help adult smokers switch from using the more unhealthy combustible tobacco.
However, critics argue that adolescents who use e-cigarettes may be more likely to try other products that deliver nicotine, which would perpetuate the current epidemic of tobacco-related illness, said Adam M. Leventhal, Ph.D., of the department of preventive medicine, University of Southern California, Los Angeles, and his associates.
The investigators analyzed data from a longitudinal survey of substance use and mental health among high school students. In their prospective observational study, they focused on 2,530 demographically diverse students in ninth grade at 10 Los Angeles–area public high schools. The students were nonsmokers at baseline. A total of 222 of these adolescents reported that they had used e-cigarettes, while 2,308 had not.
Adolescents who had used e-cigarettes were much more likely than were nonusers to report trying combustible tobacco products during the next 6 months (30.7% vs 8.1%) and during the next 12 months (25.2% vs 9.3%), for an odds ratio of 4.27 averaged across the two study periods. This association was strong for each of the combustible tobacco products assessed, with an OR of 2.65 for regular cigarettes, an OR of 4.85 for full-size cigars or cigarillos, and an OR of 3.25 for hookahs.
When the data were adjusted to account for many sociodemographic, environmental, and intrapersonal characteristics known to influence smoking, the ORs declined but the associations remained strong and statistically significant, ranging from 1.75 to 2.96, depending on the smoking product, Dr. Leventhal and his associates said (JAMA. 2015;314[7]:700-707). One possible explanation for these findings is that adolescents who used e-cigarettes enjoyed the experience and were more likely to experiment with other nicotine-containing products. However, “because this is an observational study, and one of the first to address this issue, inferences regarding whether this association is or is not causal cannot yet be made,” they noted.
Ninth-graders who have used electronic cigarettes are much more likely than are nonusers to try regular cigarettes, cigars, and hookahs during the subsequent year, according to a report published online Aug. 18 in JAMA.
E-cigarettes are handheld battery-operated devices that heat a liquid composed of nicotine, propylene glycol or glycerin, flavorings, and other chemicals to create a vapor that is inhaled, simulating the experience of cigarette smoking. Their main potential benefit is to help adult smokers switch from using the more unhealthy combustible tobacco.
However, critics argue that adolescents who use e-cigarettes may be more likely to try other products that deliver nicotine, which would perpetuate the current epidemic of tobacco-related illness, said Adam M. Leventhal, Ph.D., of the department of preventive medicine, University of Southern California, Los Angeles, and his associates.
The investigators analyzed data from a longitudinal survey of substance use and mental health among high school students. In their prospective observational study, they focused on 2,530 demographically diverse students in ninth grade at 10 Los Angeles–area public high schools. The students were nonsmokers at baseline. A total of 222 of these adolescents reported that they had used e-cigarettes, while 2,308 had not.
Adolescents who had used e-cigarettes were much more likely than were nonusers to report trying combustible tobacco products during the next 6 months (30.7% vs 8.1%) and during the next 12 months (25.2% vs 9.3%), for an odds ratio of 4.27 averaged across the two study periods. This association was strong for each of the combustible tobacco products assessed, with an OR of 2.65 for regular cigarettes, an OR of 4.85 for full-size cigars or cigarillos, and an OR of 3.25 for hookahs.
When the data were adjusted to account for many sociodemographic, environmental, and intrapersonal characteristics known to influence smoking, the ORs declined but the associations remained strong and statistically significant, ranging from 1.75 to 2.96, depending on the smoking product, Dr. Leventhal and his associates said (JAMA. 2015;314[7]:700-707). One possible explanation for these findings is that adolescents who used e-cigarettes enjoyed the experience and were more likely to experiment with other nicotine-containing products. However, “because this is an observational study, and one of the first to address this issue, inferences regarding whether this association is or is not causal cannot yet be made,” they noted.
FROM JAMA
Key clinical point: Ninth-graders who use electronic cigarettes are much more likely than are nonusers to try regular cigarettes, cigars, and hookahs during the following year.
Major finding: Adolescents who had used e-cigarettes were much more likely than were nonusers to report trying combustible tobacco products during the next 6 months (30.7% vs. 8.1%) and during the next 12 months (25.2% vs. 9.3%), for an OR of 4.27 averaged across the two study periods.
Data source: A prospective observational study of 2,530 demographically diverse, nonsmoking ninth-graders at 10 Los Angeles public high schools who were followed up for 1 year.
Disclosures: The National Institutes of Health supported the study. Dr. Leventhal and his associates reported having no relevant disclosures.
Add-on liraglutide effective in obese diabetes patients
Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.
The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.
This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.
The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.
Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).
In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A1c level; in the proportion of patients achieving HbA1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.
Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.
Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m2 or greater and in overweight adults with a BMI of 27 kg/m2 or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”
SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.
*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.
Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.
The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.
This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.
The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.
Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).
In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A1c level; in the proportion of patients achieving HbA1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.
Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.
Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m2 or greater and in overweight adults with a BMI of 27 kg/m2 or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”
SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.
*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.
Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.
The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.
This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.
The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.
Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).
In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A1c level; in the proportion of patients achieving HbA1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.
Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.
Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m2 or greater and in overweight adults with a BMI of 27 kg/m2 or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”
SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.
*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.
FROM JAMA
Key clinical point: Liraglutide, along with diet and exercise, improved weight loss and glycemic control in obese patients with type 2 diabetes.
Major finding: Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo.
Data source: SCALE Diabetes, an international randomized double-blind placebo-controlled clinical trial involving 846 participants treated for 56 weeks and followed for an additional 12 weeks.
Disclosures: SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.
Ipilimumab’s immune-related adverse effects greater in ‘real-world patients’
Patients treated with ipilimumab for metastatic melanoma should be prepared for immune-related adverse effects, and physicians should expect to treat them early and aggressively, according to a report published online Aug. 17 in Journal of Clinical Oncology.
Severe immune-related adverse effects such as diarrhea, hepatitis, and hypophysitis were common in a retrospective analysis of the medical records of 298 patients treated during a 27-month period at Memorial Sloan Kettering Cancer Center, New York. Corticosteroids were not adequate to control symptoms in a substantial number of cases, and additional systemic immunosuppressive therapy was required, said Dr. Troy Z. Horvat of Memorial Sloan Kettering and his associates.
From their institutional experience, the investigators suspected that the incidence of clinically significant adverse effects of ipilimumab was higher than has been previously reported and higher than would be expected just by counting the number of events qualifying as grade 3 or higher by National Cancer Institute criteria. They also suspected that the need for immunosuppressive therapy was greater than generally expected. Previous studies showed adverse event rates ranging from 6% to 19%, and did not give any information regarding corticosteroid use.
Their analysis confirmed these suspicions, showing that 31% of patients developed grade 3, 4, or 5 adverse effects and 35% required corticosteroid therapy. This is more than twice the rate of grade 3 or higher toxicity reported in clinical trials of ipilimumab. Adverse effects included diarrhea (50 patients), which led to bowel perforation in 3 patients; hepatitis (22 patients); dermatitis (21 patients); endocrinopathies (14); hypophysitis (6); uveitis (2); pneumonitis (1); seizure (1); arthritis (1); and hearing loss (1). These effects were severe enough to cause 19% of patients to discontinue ipilimumab.
About one-third of the patients who received systemic corticosteroids – 10% of the total study population – required additional immunotherapy, including infliximab, mycophenolate, or adalimumab, Dr. Horvat and his associates said (J Clin Oncol 2015 Aug 17 [doi:10.1200/JCO.2015.60.8448]).
This study’s higher rates of adverse events, of corticosteroid therapy, and of further immunosuppressive therapy are likely attributable to the treatment team’s considerable experience with ipilimumab in real-world patients. As clinicians gain such experience, they become more familiar with associated adverse events, allowing earlier identification and intervention, the investigators said.
“In our experience, if improvement in ipilimumab-related adverse effects is not evident early in the treatment with high-dose systemic corticosteroids, more prolonged treatment rarely leads to benefit, and patients usually end up requiring infliximab anyway. ... We believe the overall risk-to-benefit ratio favors the early use of infliximab rather than prolonged treatment with corticosteroids,” they noted.
The median overall survival and median time to treatment failure were not affected by either the occurrence of adverse events or the use of corticosteroids. Overall, 12% of these patients achieved long-term disease control and didn’t require further melanoma treatment. Based on their findings and those of another research group, “we believe that patients and physicians should not be concerned that ipilimumab-related adverse events requiring systemic immunosuppression will compromise the therapeutic benefit,” Dr. Horvat and his associates said.
Patients treated with ipilimumab for metastatic melanoma should be prepared for immune-related adverse effects, and physicians should expect to treat them early and aggressively, according to a report published online Aug. 17 in Journal of Clinical Oncology.
Severe immune-related adverse effects such as diarrhea, hepatitis, and hypophysitis were common in a retrospective analysis of the medical records of 298 patients treated during a 27-month period at Memorial Sloan Kettering Cancer Center, New York. Corticosteroids were not adequate to control symptoms in a substantial number of cases, and additional systemic immunosuppressive therapy was required, said Dr. Troy Z. Horvat of Memorial Sloan Kettering and his associates.
From their institutional experience, the investigators suspected that the incidence of clinically significant adverse effects of ipilimumab was higher than has been previously reported and higher than would be expected just by counting the number of events qualifying as grade 3 or higher by National Cancer Institute criteria. They also suspected that the need for immunosuppressive therapy was greater than generally expected. Previous studies showed adverse event rates ranging from 6% to 19%, and did not give any information regarding corticosteroid use.
Their analysis confirmed these suspicions, showing that 31% of patients developed grade 3, 4, or 5 adverse effects and 35% required corticosteroid therapy. This is more than twice the rate of grade 3 or higher toxicity reported in clinical trials of ipilimumab. Adverse effects included diarrhea (50 patients), which led to bowel perforation in 3 patients; hepatitis (22 patients); dermatitis (21 patients); endocrinopathies (14); hypophysitis (6); uveitis (2); pneumonitis (1); seizure (1); arthritis (1); and hearing loss (1). These effects were severe enough to cause 19% of patients to discontinue ipilimumab.
About one-third of the patients who received systemic corticosteroids – 10% of the total study population – required additional immunotherapy, including infliximab, mycophenolate, or adalimumab, Dr. Horvat and his associates said (J Clin Oncol 2015 Aug 17 [doi:10.1200/JCO.2015.60.8448]).
This study’s higher rates of adverse events, of corticosteroid therapy, and of further immunosuppressive therapy are likely attributable to the treatment team’s considerable experience with ipilimumab in real-world patients. As clinicians gain such experience, they become more familiar with associated adverse events, allowing earlier identification and intervention, the investigators said.
“In our experience, if improvement in ipilimumab-related adverse effects is not evident early in the treatment with high-dose systemic corticosteroids, more prolonged treatment rarely leads to benefit, and patients usually end up requiring infliximab anyway. ... We believe the overall risk-to-benefit ratio favors the early use of infliximab rather than prolonged treatment with corticosteroids,” they noted.
The median overall survival and median time to treatment failure were not affected by either the occurrence of adverse events or the use of corticosteroids. Overall, 12% of these patients achieved long-term disease control and didn’t require further melanoma treatment. Based on their findings and those of another research group, “we believe that patients and physicians should not be concerned that ipilimumab-related adverse events requiring systemic immunosuppression will compromise the therapeutic benefit,” Dr. Horvat and his associates said.
Patients treated with ipilimumab for metastatic melanoma should be prepared for immune-related adverse effects, and physicians should expect to treat them early and aggressively, according to a report published online Aug. 17 in Journal of Clinical Oncology.
Severe immune-related adverse effects such as diarrhea, hepatitis, and hypophysitis were common in a retrospective analysis of the medical records of 298 patients treated during a 27-month period at Memorial Sloan Kettering Cancer Center, New York. Corticosteroids were not adequate to control symptoms in a substantial number of cases, and additional systemic immunosuppressive therapy was required, said Dr. Troy Z. Horvat of Memorial Sloan Kettering and his associates.
From their institutional experience, the investigators suspected that the incidence of clinically significant adverse effects of ipilimumab was higher than has been previously reported and higher than would be expected just by counting the number of events qualifying as grade 3 or higher by National Cancer Institute criteria. They also suspected that the need for immunosuppressive therapy was greater than generally expected. Previous studies showed adverse event rates ranging from 6% to 19%, and did not give any information regarding corticosteroid use.
Their analysis confirmed these suspicions, showing that 31% of patients developed grade 3, 4, or 5 adverse effects and 35% required corticosteroid therapy. This is more than twice the rate of grade 3 or higher toxicity reported in clinical trials of ipilimumab. Adverse effects included diarrhea (50 patients), which led to bowel perforation in 3 patients; hepatitis (22 patients); dermatitis (21 patients); endocrinopathies (14); hypophysitis (6); uveitis (2); pneumonitis (1); seizure (1); arthritis (1); and hearing loss (1). These effects were severe enough to cause 19% of patients to discontinue ipilimumab.
About one-third of the patients who received systemic corticosteroids – 10% of the total study population – required additional immunotherapy, including infliximab, mycophenolate, or adalimumab, Dr. Horvat and his associates said (J Clin Oncol 2015 Aug 17 [doi:10.1200/JCO.2015.60.8448]).
This study’s higher rates of adverse events, of corticosteroid therapy, and of further immunosuppressive therapy are likely attributable to the treatment team’s considerable experience with ipilimumab in real-world patients. As clinicians gain such experience, they become more familiar with associated adverse events, allowing earlier identification and intervention, the investigators said.
“In our experience, if improvement in ipilimumab-related adverse effects is not evident early in the treatment with high-dose systemic corticosteroids, more prolonged treatment rarely leads to benefit, and patients usually end up requiring infliximab anyway. ... We believe the overall risk-to-benefit ratio favors the early use of infliximab rather than prolonged treatment with corticosteroids,” they noted.
The median overall survival and median time to treatment failure were not affected by either the occurrence of adverse events or the use of corticosteroids. Overall, 12% of these patients achieved long-term disease control and didn’t require further melanoma treatment. Based on their findings and those of another research group, “we believe that patients and physicians should not be concerned that ipilimumab-related adverse events requiring systemic immunosuppression will compromise the therapeutic benefit,” Dr. Horvat and his associates said.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Physicians and patients should be prepared for immune-related adverse effects from ipilimumab for treatment of metastatic melanoma.
Major finding: Just under one-third of patients developed grade 3, 4, or 5 adverse effects and 35% of patients required corticosteroid therapy, more than twice the rate of grade 3 or higher toxicity reported in clinical trials of ipilimumab.
Data source: A single-center retrospective analysis of adverse effects from ipilimumab therapy in 298 patients treated during a 27-month period.
Disclosures: This study was supported in part by the John K. Figge Fund. Dr. Horvat reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.