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APA guideline stresses judicious antipsychotics in dementia
Antipsychotics should be used judiciously when patients with dementia develop agitation or psychosis, according to the American Psychiatric Association’s first practice guideline on this issue published May 1 in the American Journal of Psychiatry.
Most patients with dementia develop psychosis or agitation during their illness, and treatment, based on expert consensus, often has involved antipsychotics. Antipsychotics have been thought to minimize the risk of violence, reduce patient distress, improve the patient’s quality of life, and reduce the burden on caregivers. But recent clinical trial results suggest that the benefits in this patient population are small at best, while the harms – including increased mortality and accelerated cognitive decline – are significant, said Dr. Victor I. Reus, chair of the APA Practice Guideline Writing Group and his associates.
The group developed this guideline based on a systematic review of the evidence, including results of a survey of experts in the treatment of agitation or psychosis in people with dementia. Overall, the guideline’s 15 recommendations stress that these medications must be just one part of a comprehensive, patient-centered treatment plan that includes both drug and nondrug components, said Dr. Reus, also professor of psychiatry at the University of California, San Francisco, and his associates.
Among the new recommendations, the APA emphasizes that antipsychotics should be used only when agitation or psychosis are severe, dangerous, and/or cause the patient significant distress. The potential risks and benefits should be discussed with the patient (if feasible), family, and other caregivers.
If antipsychotic treatment is initiated, it should be started at low doses and titrated up to the minimum effective dose tolerated. Haloperidol should not be used as a first-line agent, and long-acting injectable antipsychotics should not be used unless indicated for a concomitant chronic psychotic disorder, Dr. Reus and his associates said (Am J Psychiatry. 2016;173:1-4 doi: 10.1176/appi.ajp.2015.173501).
If any side effects develop, the clinician should review all side effects, risks, and benefits, and discuss these with the patient, family, and caregivers, to determine whether tapering or discontinuing the drug is indicated.
Response to treatment should be assessed using a quantitative measure. If there is no clinically relevant response after a 4-week trial of an adequate dose of an antipsychotic medication, it should be tapered and withdrawn. If there is a positive response, eventual tapering of the drug should be discussed with the patient, family, and caregivers, including the potential risks of continued use of these agents.
Attempts to taper and withdraw the antipsychotic should commence within 4 months. Symptoms should be monitored at least monthly during drug tapering and for at least 4 months after treatment cessation to identify signs of recurrence of psychosis or agitation.
The full Guideline is available online at http://psychiatryonline.org.
Antipsychotics should be used judiciously when patients with dementia develop agitation or psychosis, according to the American Psychiatric Association’s first practice guideline on this issue published May 1 in the American Journal of Psychiatry.
Most patients with dementia develop psychosis or agitation during their illness, and treatment, based on expert consensus, often has involved antipsychotics. Antipsychotics have been thought to minimize the risk of violence, reduce patient distress, improve the patient’s quality of life, and reduce the burden on caregivers. But recent clinical trial results suggest that the benefits in this patient population are small at best, while the harms – including increased mortality and accelerated cognitive decline – are significant, said Dr. Victor I. Reus, chair of the APA Practice Guideline Writing Group and his associates.
The group developed this guideline based on a systematic review of the evidence, including results of a survey of experts in the treatment of agitation or psychosis in people with dementia. Overall, the guideline’s 15 recommendations stress that these medications must be just one part of a comprehensive, patient-centered treatment plan that includes both drug and nondrug components, said Dr. Reus, also professor of psychiatry at the University of California, San Francisco, and his associates.
Among the new recommendations, the APA emphasizes that antipsychotics should be used only when agitation or psychosis are severe, dangerous, and/or cause the patient significant distress. The potential risks and benefits should be discussed with the patient (if feasible), family, and other caregivers.
If antipsychotic treatment is initiated, it should be started at low doses and titrated up to the minimum effective dose tolerated. Haloperidol should not be used as a first-line agent, and long-acting injectable antipsychotics should not be used unless indicated for a concomitant chronic psychotic disorder, Dr. Reus and his associates said (Am J Psychiatry. 2016;173:1-4 doi: 10.1176/appi.ajp.2015.173501).
If any side effects develop, the clinician should review all side effects, risks, and benefits, and discuss these with the patient, family, and caregivers, to determine whether tapering or discontinuing the drug is indicated.
Response to treatment should be assessed using a quantitative measure. If there is no clinically relevant response after a 4-week trial of an adequate dose of an antipsychotic medication, it should be tapered and withdrawn. If there is a positive response, eventual tapering of the drug should be discussed with the patient, family, and caregivers, including the potential risks of continued use of these agents.
Attempts to taper and withdraw the antipsychotic should commence within 4 months. Symptoms should be monitored at least monthly during drug tapering and for at least 4 months after treatment cessation to identify signs of recurrence of psychosis or agitation.
The full Guideline is available online at http://psychiatryonline.org.
Antipsychotics should be used judiciously when patients with dementia develop agitation or psychosis, according to the American Psychiatric Association’s first practice guideline on this issue published May 1 in the American Journal of Psychiatry.
Most patients with dementia develop psychosis or agitation during their illness, and treatment, based on expert consensus, often has involved antipsychotics. Antipsychotics have been thought to minimize the risk of violence, reduce patient distress, improve the patient’s quality of life, and reduce the burden on caregivers. But recent clinical trial results suggest that the benefits in this patient population are small at best, while the harms – including increased mortality and accelerated cognitive decline – are significant, said Dr. Victor I. Reus, chair of the APA Practice Guideline Writing Group and his associates.
The group developed this guideline based on a systematic review of the evidence, including results of a survey of experts in the treatment of agitation or psychosis in people with dementia. Overall, the guideline’s 15 recommendations stress that these medications must be just one part of a comprehensive, patient-centered treatment plan that includes both drug and nondrug components, said Dr. Reus, also professor of psychiatry at the University of California, San Francisco, and his associates.
Among the new recommendations, the APA emphasizes that antipsychotics should be used only when agitation or psychosis are severe, dangerous, and/or cause the patient significant distress. The potential risks and benefits should be discussed with the patient (if feasible), family, and other caregivers.
If antipsychotic treatment is initiated, it should be started at low doses and titrated up to the minimum effective dose tolerated. Haloperidol should not be used as a first-line agent, and long-acting injectable antipsychotics should not be used unless indicated for a concomitant chronic psychotic disorder, Dr. Reus and his associates said (Am J Psychiatry. 2016;173:1-4 doi: 10.1176/appi.ajp.2015.173501).
If any side effects develop, the clinician should review all side effects, risks, and benefits, and discuss these with the patient, family, and caregivers, to determine whether tapering or discontinuing the drug is indicated.
Response to treatment should be assessed using a quantitative measure. If there is no clinically relevant response after a 4-week trial of an adequate dose of an antipsychotic medication, it should be tapered and withdrawn. If there is a positive response, eventual tapering of the drug should be discussed with the patient, family, and caregivers, including the potential risks of continued use of these agents.
Attempts to taper and withdraw the antipsychotic should commence within 4 months. Symptoms should be monitored at least monthly during drug tapering and for at least 4 months after treatment cessation to identify signs of recurrence of psychosis or agitation.
The full Guideline is available online at http://psychiatryonline.org.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
Key clinical point: Antipsychotics should be used only when agitation or psychosis are severe, dangerous, and/or cause significant distress for dementia patients.
Major finding: The guideline’s 15 recommendations stress that these medications must be just one part of a comprehensive, patient-centered treatment plan that includes drug and nondrug components.
Data source: A review of the evidence and compilation of a new clinical practice guideline with 15 recommendations.
Disclosures: This guideline was developed by the APA Practice Guideline Writing Group. No financial disclosures were provided.
Physicians ‘upcoding’ anesthesia risk during outpatient endoscopy?
Gastrointestinal endoscopists appear to be “upcoding” patient anesthesia risk during outpatient procedures so that health insurance will cover the cost of anesthesia services such as sedation, according to a research letter to the editor published online May 2 in JAMA Internal Medicine.
Many have noted a recent, substantial increase in the use of anesthesia services for outpatient endoscopies, but the reason for this rise is unclear. Some argue that patient anesthesia-related risk has increased, possibly because of an increase in endoscopy patients’ comorbidities such as obesity, sleep apnea, asthma, and cardiovascular or pulmonary disorders. Others argue that clinicians are exaggerating patient risk because anesthesia services often are covered only in patients for whom sedation or anesthesia carries a high risk of complications, said Xiaoyu Nie, a doctoral candidate and assistant policy analyst at Rand Corp., Santa Monica (Calif.), and her associates.
The investigators analyzed time trends in insurance claims for anesthesia services during upper endoscopy or colonoscopy procedures at private offices, hospital outpatient clinics, ambulatory surgical centers, or other outpatient sites. They focused on 1,001,841 claims made for adults during a recent 8-year period (JAMA Intern Med. 2016 May 2. doi: 10.1001/jamainternmen.2016.1244).
The probability of being coded as having high risk of anesthesia complications more than doubled during this period. The percentage of patients categorized as high risk rose from 11.6% of the approximately 22,297 patients treated during the first year of the study period (2005) to 18.9% of the 207,117 patients so categorized during the final year (2013). Yet patient clinical characteristics, notably their comorbidities, did not change significantly, indicating that their actual risk did not increase.
The most likely explanation for this change is that “physicians used their clinical discretion to systematically change coding practices because coding a patient as being at high risk in a claim ensures payment of the claim,” Ms. Nie and her associates said.
Gastrointestinal endoscopists appear to be “upcoding” patient anesthesia risk during outpatient procedures so that health insurance will cover the cost of anesthesia services such as sedation, according to a research letter to the editor published online May 2 in JAMA Internal Medicine.
Many have noted a recent, substantial increase in the use of anesthesia services for outpatient endoscopies, but the reason for this rise is unclear. Some argue that patient anesthesia-related risk has increased, possibly because of an increase in endoscopy patients’ comorbidities such as obesity, sleep apnea, asthma, and cardiovascular or pulmonary disorders. Others argue that clinicians are exaggerating patient risk because anesthesia services often are covered only in patients for whom sedation or anesthesia carries a high risk of complications, said Xiaoyu Nie, a doctoral candidate and assistant policy analyst at Rand Corp., Santa Monica (Calif.), and her associates.
The investigators analyzed time trends in insurance claims for anesthesia services during upper endoscopy or colonoscopy procedures at private offices, hospital outpatient clinics, ambulatory surgical centers, or other outpatient sites. They focused on 1,001,841 claims made for adults during a recent 8-year period (JAMA Intern Med. 2016 May 2. doi: 10.1001/jamainternmen.2016.1244).
The probability of being coded as having high risk of anesthesia complications more than doubled during this period. The percentage of patients categorized as high risk rose from 11.6% of the approximately 22,297 patients treated during the first year of the study period (2005) to 18.9% of the 207,117 patients so categorized during the final year (2013). Yet patient clinical characteristics, notably their comorbidities, did not change significantly, indicating that their actual risk did not increase.
The most likely explanation for this change is that “physicians used their clinical discretion to systematically change coding practices because coding a patient as being at high risk in a claim ensures payment of the claim,” Ms. Nie and her associates said.
Gastrointestinal endoscopists appear to be “upcoding” patient anesthesia risk during outpatient procedures so that health insurance will cover the cost of anesthesia services such as sedation, according to a research letter to the editor published online May 2 in JAMA Internal Medicine.
Many have noted a recent, substantial increase in the use of anesthesia services for outpatient endoscopies, but the reason for this rise is unclear. Some argue that patient anesthesia-related risk has increased, possibly because of an increase in endoscopy patients’ comorbidities such as obesity, sleep apnea, asthma, and cardiovascular or pulmonary disorders. Others argue that clinicians are exaggerating patient risk because anesthesia services often are covered only in patients for whom sedation or anesthesia carries a high risk of complications, said Xiaoyu Nie, a doctoral candidate and assistant policy analyst at Rand Corp., Santa Monica (Calif.), and her associates.
The investigators analyzed time trends in insurance claims for anesthesia services during upper endoscopy or colonoscopy procedures at private offices, hospital outpatient clinics, ambulatory surgical centers, or other outpatient sites. They focused on 1,001,841 claims made for adults during a recent 8-year period (JAMA Intern Med. 2016 May 2. doi: 10.1001/jamainternmen.2016.1244).
The probability of being coded as having high risk of anesthesia complications more than doubled during this period. The percentage of patients categorized as high risk rose from 11.6% of the approximately 22,297 patients treated during the first year of the study period (2005) to 18.9% of the 207,117 patients so categorized during the final year (2013). Yet patient clinical characteristics, notably their comorbidities, did not change significantly, indicating that their actual risk did not increase.
The most likely explanation for this change is that “physicians used their clinical discretion to systematically change coding practices because coding a patient as being at high risk in a claim ensures payment of the claim,” Ms. Nie and her associates said.
FROM JAMA INTERNAL MEDICINE
Key clinical point: GI endoscopists appear to be “upcoding” patient anesthesia risk so health insurance will cover the cost of anesthesia services.
Major finding: The percentage of patients categorized as high risk rose from 11.6% of the approximately 23,000 patients treated in 2005 to 18.9% of the 207,117 patients so categorized in 2013.
Data source: An analysis of time trends involving more than 1 million anesthesia claims made during an 8-year period.
Disclosures: This study was supported by Ethicon Endo-Surgery. Ms. Nie and her associates reported having no relevant financial disclosures.
Hospital intervention slashes heparin-induced thrombocytopenia
A simple, hospital-wide “avoid heparin” intervention dramatically cut the rate of suspected heparin-induced thrombocytopenia by 42%, that of positive ELISA screens for HIT by 63%, that of adjudicated HIT by 79%, and that of HIT with thrombosis by 91%, while also reducing the costs of HIT-related care by 83% at one large university hospital.
The medical literature has focused on early recognition and treatment of heparin-induced thrombocytopenia, “but its prevention has been largely overlooked,” noted Dr. Kelly E. McGowan of Sunnybrook Health Sciences Centre and the University of Toronto and her associates.
Sunnybrook introduced an “avoid heparin” program in 2006 in which most intravenous and subcutaneous unfractionated heparin was replaced with low-molecular-weight heparin (LMWH) in prophylactic or therapeutic doses; heparinized saline in arterial and central venous lines was replaced with saline flushes; order sets were modified to exclude unfractionated heparin options; and unfractionated heparin stores were removed from most nursing units.
Unfractionated heparin remained available for use in hemodialysis, cardiovascular surgery, and certain cases of acute coronary syndrome. Most hospital clinicians were unaware that LMWH was being substituted for unfractionated heparin, and none were aware that the effects of this change were being studied.
The investigators assessed all 1,118 cases of suspected heparin-induced thrombocytopenia that occurred during a 10-year period before and after this intervention was implemented. The use of LMWH rose fourfold after the program was initiated, but the annual rate of HIT associated with LMWH remained constant at 0.9 cases per 10,000 admissions over the course of the study.
The annual incidence of suspected HIT decreased from 85.5 per 10,000 admissions per year before the intervention to 49.0 afterward (relative risk reduction, 41.7%). The rate of positive ELISA screens for the disorder dropped from 16.5 to 6.1 per 10,000 (RRR, 62.9%), the rate of adjudicated HIT decreased from 10.7 to 2.2 per 10,000, and the rate of HIT with thrombosis declined from 4.6 to 0.4 per 10,000.
The program’s greatest impact was on cardiac surgery, but the burden of HIT also markedly decreased in other surgical and medical patients. HIT decreased by 77% in cardiovascular surgeries, 77% in other surgeries, 75% in cardiology patients, and 62% in medical patients, Dr. McGowan and her associates said (Blood 2016 Apr 21;127[16]:1954-9).
Patients with HIT during the preintervention years more often developed thrombosis (43%), usually venous thromboembolism, compared with those who had HIT in the postintervention years (19%), and median length of stay declined accordingly. The average estimated costs of HIT care per year dropped by about $267,000 dollars per year, from $322,000 before the program was implemented to $55,000 afterward.
The investigators added that this is the first study ever to show the success of an HIT prevention strategy. Their findings indicate that a hospital-wide “avoid heparin” program can substantially reduce morbidity, mortality, and costs associated with HIT. “The heparin avoidance strategy that we used was not complex or costly and would be feasible in other centers,” they noted.
This study is the first to show the substantial impact of large-scale removal of heparin from clinical practice in the real world. But implementing such a program at a system-wide level wouldn’t be simple.
The cost of a unit of low-molecular-weight heparin is six- to eightfold higher than that of unfractionated heparin. Hospitals may need to be convinced that unfractionated heparin is not the bargain it appears to be once the costs of heparin-induced thrombocytopenia are factored in.
In addition, unfractionated heparin remains the best option for patients undergoing cardiovascular surgery, those with renal failure, and those at high risk for bleeding that requires a rapid reversal agent.
Lori-Ann Linkins, M.D., of McMaster University, Hamilton (Ont.), made these remarks in a commentary accompanying Dr. McGowan’s report (Blood 2016 Apr 21;127[16]:1945-6). She reported receiving lecture honoraria from Pfizer and research funding from Bayer.
This study is the first to show the substantial impact of large-scale removal of heparin from clinical practice in the real world. But implementing such a program at a system-wide level wouldn’t be simple.
The cost of a unit of low-molecular-weight heparin is six- to eightfold higher than that of unfractionated heparin. Hospitals may need to be convinced that unfractionated heparin is not the bargain it appears to be once the costs of heparin-induced thrombocytopenia are factored in.
In addition, unfractionated heparin remains the best option for patients undergoing cardiovascular surgery, those with renal failure, and those at high risk for bleeding that requires a rapid reversal agent.
Lori-Ann Linkins, M.D., of McMaster University, Hamilton (Ont.), made these remarks in a commentary accompanying Dr. McGowan’s report (Blood 2016 Apr 21;127[16]:1945-6). She reported receiving lecture honoraria from Pfizer and research funding from Bayer.
This study is the first to show the substantial impact of large-scale removal of heparin from clinical practice in the real world. But implementing such a program at a system-wide level wouldn’t be simple.
The cost of a unit of low-molecular-weight heparin is six- to eightfold higher than that of unfractionated heparin. Hospitals may need to be convinced that unfractionated heparin is not the bargain it appears to be once the costs of heparin-induced thrombocytopenia are factored in.
In addition, unfractionated heparin remains the best option for patients undergoing cardiovascular surgery, those with renal failure, and those at high risk for bleeding that requires a rapid reversal agent.
Lori-Ann Linkins, M.D., of McMaster University, Hamilton (Ont.), made these remarks in a commentary accompanying Dr. McGowan’s report (Blood 2016 Apr 21;127[16]:1945-6). She reported receiving lecture honoraria from Pfizer and research funding from Bayer.
A simple, hospital-wide “avoid heparin” intervention dramatically cut the rate of suspected heparin-induced thrombocytopenia by 42%, that of positive ELISA screens for HIT by 63%, that of adjudicated HIT by 79%, and that of HIT with thrombosis by 91%, while also reducing the costs of HIT-related care by 83% at one large university hospital.
The medical literature has focused on early recognition and treatment of heparin-induced thrombocytopenia, “but its prevention has been largely overlooked,” noted Dr. Kelly E. McGowan of Sunnybrook Health Sciences Centre and the University of Toronto and her associates.
Sunnybrook introduced an “avoid heparin” program in 2006 in which most intravenous and subcutaneous unfractionated heparin was replaced with low-molecular-weight heparin (LMWH) in prophylactic or therapeutic doses; heparinized saline in arterial and central venous lines was replaced with saline flushes; order sets were modified to exclude unfractionated heparin options; and unfractionated heparin stores were removed from most nursing units.
Unfractionated heparin remained available for use in hemodialysis, cardiovascular surgery, and certain cases of acute coronary syndrome. Most hospital clinicians were unaware that LMWH was being substituted for unfractionated heparin, and none were aware that the effects of this change were being studied.
The investigators assessed all 1,118 cases of suspected heparin-induced thrombocytopenia that occurred during a 10-year period before and after this intervention was implemented. The use of LMWH rose fourfold after the program was initiated, but the annual rate of HIT associated with LMWH remained constant at 0.9 cases per 10,000 admissions over the course of the study.
The annual incidence of suspected HIT decreased from 85.5 per 10,000 admissions per year before the intervention to 49.0 afterward (relative risk reduction, 41.7%). The rate of positive ELISA screens for the disorder dropped from 16.5 to 6.1 per 10,000 (RRR, 62.9%), the rate of adjudicated HIT decreased from 10.7 to 2.2 per 10,000, and the rate of HIT with thrombosis declined from 4.6 to 0.4 per 10,000.
The program’s greatest impact was on cardiac surgery, but the burden of HIT also markedly decreased in other surgical and medical patients. HIT decreased by 77% in cardiovascular surgeries, 77% in other surgeries, 75% in cardiology patients, and 62% in medical patients, Dr. McGowan and her associates said (Blood 2016 Apr 21;127[16]:1954-9).
Patients with HIT during the preintervention years more often developed thrombosis (43%), usually venous thromboembolism, compared with those who had HIT in the postintervention years (19%), and median length of stay declined accordingly. The average estimated costs of HIT care per year dropped by about $267,000 dollars per year, from $322,000 before the program was implemented to $55,000 afterward.
The investigators added that this is the first study ever to show the success of an HIT prevention strategy. Their findings indicate that a hospital-wide “avoid heparin” program can substantially reduce morbidity, mortality, and costs associated with HIT. “The heparin avoidance strategy that we used was not complex or costly and would be feasible in other centers,” they noted.
A simple, hospital-wide “avoid heparin” intervention dramatically cut the rate of suspected heparin-induced thrombocytopenia by 42%, that of positive ELISA screens for HIT by 63%, that of adjudicated HIT by 79%, and that of HIT with thrombosis by 91%, while also reducing the costs of HIT-related care by 83% at one large university hospital.
The medical literature has focused on early recognition and treatment of heparin-induced thrombocytopenia, “but its prevention has been largely overlooked,” noted Dr. Kelly E. McGowan of Sunnybrook Health Sciences Centre and the University of Toronto and her associates.
Sunnybrook introduced an “avoid heparin” program in 2006 in which most intravenous and subcutaneous unfractionated heparin was replaced with low-molecular-weight heparin (LMWH) in prophylactic or therapeutic doses; heparinized saline in arterial and central venous lines was replaced with saline flushes; order sets were modified to exclude unfractionated heparin options; and unfractionated heparin stores were removed from most nursing units.
Unfractionated heparin remained available for use in hemodialysis, cardiovascular surgery, and certain cases of acute coronary syndrome. Most hospital clinicians were unaware that LMWH was being substituted for unfractionated heparin, and none were aware that the effects of this change were being studied.
The investigators assessed all 1,118 cases of suspected heparin-induced thrombocytopenia that occurred during a 10-year period before and after this intervention was implemented. The use of LMWH rose fourfold after the program was initiated, but the annual rate of HIT associated with LMWH remained constant at 0.9 cases per 10,000 admissions over the course of the study.
The annual incidence of suspected HIT decreased from 85.5 per 10,000 admissions per year before the intervention to 49.0 afterward (relative risk reduction, 41.7%). The rate of positive ELISA screens for the disorder dropped from 16.5 to 6.1 per 10,000 (RRR, 62.9%), the rate of adjudicated HIT decreased from 10.7 to 2.2 per 10,000, and the rate of HIT with thrombosis declined from 4.6 to 0.4 per 10,000.
The program’s greatest impact was on cardiac surgery, but the burden of HIT also markedly decreased in other surgical and medical patients. HIT decreased by 77% in cardiovascular surgeries, 77% in other surgeries, 75% in cardiology patients, and 62% in medical patients, Dr. McGowan and her associates said (Blood 2016 Apr 21;127[16]:1954-9).
Patients with HIT during the preintervention years more often developed thrombosis (43%), usually venous thromboembolism, compared with those who had HIT in the postintervention years (19%), and median length of stay declined accordingly. The average estimated costs of HIT care per year dropped by about $267,000 dollars per year, from $322,000 before the program was implemented to $55,000 afterward.
The investigators added that this is the first study ever to show the success of an HIT prevention strategy. Their findings indicate that a hospital-wide “avoid heparin” program can substantially reduce morbidity, mortality, and costs associated with HIT. “The heparin avoidance strategy that we used was not complex or costly and would be feasible in other centers,” they noted.
FROM BLOOD
Key clinical point: A simple, hospital-wide “avoid heparin” intervention dramatically cut the burden of heparin-induced thrombocytopenia at one hospital.
Major finding: The annual incidence of suspected HIT decreased from 85.5 per 10,000 admissions per year before the intervention to 49.0 afterward (relative risk reduction, 41.7%).
Data source: A retrospective comparison of 1,118 heparin-induced disorders at a large university hospital before and after the implementation of a preventive intervention.
Disclosures: No sponsors/supporters were identified for this study. Dr. McGowan reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.
Many ‘nonurgent’ ED cases actually are urgent
Many emergency department cases deemed “nonurgent” by triage personnel actually are indistinguishable from those deemed “urgent,” according to a Research Letter to the Editor published in JAMA Internal Medicine.
To examine whether a triage determination of nonurgent status really rules out the possibility of serious pathology, researchers analyzed data from the National Hospital Ambulatory Medical Care Survey, a representative annual probability sample survey of ED visits categorized by level of urgency. They focused on 59,293 ED visits by patients aged 18-64 years during a 3-year period, which were representative of 240 million ED visits across the country. An estimated total of 218.5 million of these visits (92.5%) were categorized as urgent and 17.8 million (7.5%) as nonurgent by triage personnel, said Dr. Renee Y. Hsia of the department of emergency medicine and the Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, and her associates.
Patients required diagnostic services such as blood tests, electrocardiograms, or imaging in 8.45 million “nonurgent” visits (48%), and patients required procedures such as intravenous fluids, casting, or splinting in 5.76 million “nonurgent” visits (32%). More than 775,000 “nonurgent” visits (4%) resulted in hospital admission, including 126,000 admissions to critical care units. And in 1.19 million “nonurgent” visits (7%), patients arrived by ambulance.
In addition, half of the top 10 diagnoses from “nonurgent” visits were identical to those from urgent visits, the investigators said (JAMA Int Med. 2016 April 18. doi: 10.1001/jamainternmed.2016.0878).
“Certainly, not all of these data necessarily indicate that these services were required, and they could signal overuse or a lack of availability of primary care physicians. However, to some degree, our findings indicate that either patients or health care professionals do entertain a degree of uncertainty that requires further evaluation before diagnosis,” Dr. Hsia and her associates said.
Triage was never intended to completely rule out the possibility of severe illness in patients considered nonurgent, but was meant to predict the amount of time a patient could safely wait to be seen in the ED. However, over time, “the term ‘nonurgent’ has been often politicized to mean ‘inappropriate,’ ” they noted.
“Our findings highlight the lack of certainty of nonurgent status even when it is determined prospectively by a provider at triage, and suggest that caution must be taken when using triage scores beyond their intended purpose,” the investigators said.
Many emergency department cases deemed “nonurgent” by triage personnel actually are indistinguishable from those deemed “urgent,” according to a Research Letter to the Editor published in JAMA Internal Medicine.
To examine whether a triage determination of nonurgent status really rules out the possibility of serious pathology, researchers analyzed data from the National Hospital Ambulatory Medical Care Survey, a representative annual probability sample survey of ED visits categorized by level of urgency. They focused on 59,293 ED visits by patients aged 18-64 years during a 3-year period, which were representative of 240 million ED visits across the country. An estimated total of 218.5 million of these visits (92.5%) were categorized as urgent and 17.8 million (7.5%) as nonurgent by triage personnel, said Dr. Renee Y. Hsia of the department of emergency medicine and the Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, and her associates.
Patients required diagnostic services such as blood tests, electrocardiograms, or imaging in 8.45 million “nonurgent” visits (48%), and patients required procedures such as intravenous fluids, casting, or splinting in 5.76 million “nonurgent” visits (32%). More than 775,000 “nonurgent” visits (4%) resulted in hospital admission, including 126,000 admissions to critical care units. And in 1.19 million “nonurgent” visits (7%), patients arrived by ambulance.
In addition, half of the top 10 diagnoses from “nonurgent” visits were identical to those from urgent visits, the investigators said (JAMA Int Med. 2016 April 18. doi: 10.1001/jamainternmed.2016.0878).
“Certainly, not all of these data necessarily indicate that these services were required, and they could signal overuse or a lack of availability of primary care physicians. However, to some degree, our findings indicate that either patients or health care professionals do entertain a degree of uncertainty that requires further evaluation before diagnosis,” Dr. Hsia and her associates said.
Triage was never intended to completely rule out the possibility of severe illness in patients considered nonurgent, but was meant to predict the amount of time a patient could safely wait to be seen in the ED. However, over time, “the term ‘nonurgent’ has been often politicized to mean ‘inappropriate,’ ” they noted.
“Our findings highlight the lack of certainty of nonurgent status even when it is determined prospectively by a provider at triage, and suggest that caution must be taken when using triage scores beyond their intended purpose,” the investigators said.
Many emergency department cases deemed “nonurgent” by triage personnel actually are indistinguishable from those deemed “urgent,” according to a Research Letter to the Editor published in JAMA Internal Medicine.
To examine whether a triage determination of nonurgent status really rules out the possibility of serious pathology, researchers analyzed data from the National Hospital Ambulatory Medical Care Survey, a representative annual probability sample survey of ED visits categorized by level of urgency. They focused on 59,293 ED visits by patients aged 18-64 years during a 3-year period, which were representative of 240 million ED visits across the country. An estimated total of 218.5 million of these visits (92.5%) were categorized as urgent and 17.8 million (7.5%) as nonurgent by triage personnel, said Dr. Renee Y. Hsia of the department of emergency medicine and the Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, and her associates.
Patients required diagnostic services such as blood tests, electrocardiograms, or imaging in 8.45 million “nonurgent” visits (48%), and patients required procedures such as intravenous fluids, casting, or splinting in 5.76 million “nonurgent” visits (32%). More than 775,000 “nonurgent” visits (4%) resulted in hospital admission, including 126,000 admissions to critical care units. And in 1.19 million “nonurgent” visits (7%), patients arrived by ambulance.
In addition, half of the top 10 diagnoses from “nonurgent” visits were identical to those from urgent visits, the investigators said (JAMA Int Med. 2016 April 18. doi: 10.1001/jamainternmed.2016.0878).
“Certainly, not all of these data necessarily indicate that these services were required, and they could signal overuse or a lack of availability of primary care physicians. However, to some degree, our findings indicate that either patients or health care professionals do entertain a degree of uncertainty that requires further evaluation before diagnosis,” Dr. Hsia and her associates said.
Triage was never intended to completely rule out the possibility of severe illness in patients considered nonurgent, but was meant to predict the amount of time a patient could safely wait to be seen in the ED. However, over time, “the term ‘nonurgent’ has been often politicized to mean ‘inappropriate,’ ” they noted.
“Our findings highlight the lack of certainty of nonurgent status even when it is determined prospectively by a provider at triage, and suggest that caution must be taken when using triage scores beyond their intended purpose,” the investigators said.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Many emergency department cases deemed “nonurgent” by triage personnel actually are indistinguishable from those deemed “urgent.”
Major finding: Patients required diagnostic services such as blood tests, ECGs, or imaging in 8.45 million “nonurgent” ED visits (48%), and procedures such as intravenous fluids, casting, or splinting in 5.76 million (32%).
Data source: An analysis of 59,293 adult ED visits representing 240 million such visits across the United States during a 3-year period.
Disclosures: No sponsor was identified for this study. Dr. Hsia and her associates reported having no relevant financial disclosures.
Two Ebola vaccines effective, safe in phase I trials
Two Ebola vaccines were found safe and effective in separate international phase I trials involving healthy European and African adults, according to two reports published online April 27 in the New England Journal of Medicine.
After further testing and confirmation of these preliminary results, both vaccines should prove useful in both preventing and controlling future outbreaks, both research groups said.
Several vaccines showed promise in previous primate and preliminary human studies, including one expressing the surface glycoprotein of Zaire ebolavirus (ZEBOV). Different versions of this vaccine were assessed in the present phase I studies.
In the first trial, investigators sought to extend the durability of this vaccine by administering a single “priming” dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the ZEBOV surface glycoprotein, then giving a “booster” with a modified vaccinia Ankara (MVA) strain either 1 or 2 weeks later. The participants, 60 healthy adults aged 18-50 years, were randomly assigned to receive a low dose (20 subjects), an intermediate dose (20 subjects), or a high dose (20 subjects) of viral particles. Ten participants from each of these dose groups were then offered the booster. Then two additional groups of eight participants each were assessed to see whether giving the booster at 1 week vs. at 2 weeks made a difference in immunogenicity or safety.
All the study groups showed both antibody and T-cell immunogenicity after vaccination, but the groups that received the boosters showed antibody responses four times higher than those who did not. The MVA booster increased virus-specific antibodies by a factor of 12, and significantly increased neutralizing antibodies as well, said Dr. Katie Ewer of the Jenner Institute and Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford (England) and the National Institute for Health Research Oxford Biomedical Research Centre and her associates.
The boosters also improved the vaccine’s cell-mediated immunity, increasing glycoprotein-specific CD8+ T cells by a factor of five.
In addition, the MVA booster markedly improved the vaccine’s durability, with 100% of recipients continuing to show seropositivity at 6 months, compared with only 50%-74% of participants who did not receive the booster.
The safety profile of the vaccine and the booster were termed “acceptable” at all dose levels and at all dosing intervals studied. There were no serious adverse events, and most adverse events were self-limited and mild. Moderate systemic adverse events included transient fever, myalgia, arthralgia, headache, fatigue, nausea, and malaise. Regarding laboratory abnormalities, four patients showed prolonged activated partial-thromboplastin time without coagulopathy, all of which resolved within 10 weeks; several patients showed mild or moderate lymphocytopenia and mild or moderate elevations in bilirubin, all of which were transient.
Overall, “We found that boosting can be immunogenic for antibodies and T cells at prime-boost intervals as short as 1 week. Such short-interval regimens may facilitate vaccine deployment in outbreak settings where both rapid onset and durable vaccine efficacy are required,” Dr. Ewer and her associates noted (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1411627).
They added that the ChAd3-plus-MVA viral vectors have other practical advantages. “Large-scale manufacturing processes concordant with Good Manufacturing Practice standards have been established, and both vectors have been assessed in large numbers of vaccines for a range of indications, without reports of any substantial safety concerns to date,” Dr. Ewer and her coauthors said.
The second report concerned four parallel studies: three open-label dose-escalation studies in Gabon, Kenya, and Germany and one randomized, double-blind trial in Geneva assessing the safety and immunogenicity of several doses of recombinant vesicular stomatitis virus (rVSV)-vectored ZEBOV. The 158 participants were followed for at least 6 months, said Dr. Selidji T. Agnandji of the Centre de Recherches Medicales de Lambarene (Gabon), the Institut für Tropenmedizin, Universitätsklinikum Tübingen (Germany), and the German Center for Infection Research, Tübingen, and his associates.
The vaccine was immunogenic in all participants across every dose and every study site, with higher glycoprotein-binding antibody titers at higher doses. These antibodies persisted through 6 months, a “promising” result suggesting that a single dose of this vaccine may be sufficient for early and possibly for long-term protection, the investigators said (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1502924).
Although there were no serious adverse events associated with this vaccine, acute vaccine reactions were common: 92% of patients reported an acute reaction, and 10%-22% (depending on the study site) reported grade 3 symptoms. The most bothersome – and unexpected – reactions involved viral seeding of joints and skin.
The joint problems manifested as arthritis, tenosynovitis, or bursitis that appeared at a median of 11 days after injection. The arthritis tended to affect one to four peripheral joints asymmetrically; pain was usually mild and dysfunction was usually moderate. Ten of the 11 affected patients in Geneva and both of the two (out of 60) affected patients at the other sites were symptom-free by 6 months. These findings “suggest a favorable long-term prognosis for these vaccine-induced arthritides,” Dr. Agnandji and his associates said.
Three participants developed maculopapular rashes mainly affecting the limbs, which appeared at 7-9 days following injection and persisted for 1-2 weeks. The rash was accompanied by a few tender vesicles on fingers or toes. Synovial fluid extracted from affected joints and material recovered from skin vesicles showed the presence of rVSV.
Given that most adverse reactions occurred soon after vaccination, were of short duration, and were amenable to treatment, this vaccine demonstrated “a favorable risk-benefit balance,” they added.
Two Ebola vaccines were found safe and effective in separate international phase I trials involving healthy European and African adults, according to two reports published online April 27 in the New England Journal of Medicine.
After further testing and confirmation of these preliminary results, both vaccines should prove useful in both preventing and controlling future outbreaks, both research groups said.
Several vaccines showed promise in previous primate and preliminary human studies, including one expressing the surface glycoprotein of Zaire ebolavirus (ZEBOV). Different versions of this vaccine were assessed in the present phase I studies.
In the first trial, investigators sought to extend the durability of this vaccine by administering a single “priming” dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the ZEBOV surface glycoprotein, then giving a “booster” with a modified vaccinia Ankara (MVA) strain either 1 or 2 weeks later. The participants, 60 healthy adults aged 18-50 years, were randomly assigned to receive a low dose (20 subjects), an intermediate dose (20 subjects), or a high dose (20 subjects) of viral particles. Ten participants from each of these dose groups were then offered the booster. Then two additional groups of eight participants each were assessed to see whether giving the booster at 1 week vs. at 2 weeks made a difference in immunogenicity or safety.
All the study groups showed both antibody and T-cell immunogenicity after vaccination, but the groups that received the boosters showed antibody responses four times higher than those who did not. The MVA booster increased virus-specific antibodies by a factor of 12, and significantly increased neutralizing antibodies as well, said Dr. Katie Ewer of the Jenner Institute and Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford (England) and the National Institute for Health Research Oxford Biomedical Research Centre and her associates.
The boosters also improved the vaccine’s cell-mediated immunity, increasing glycoprotein-specific CD8+ T cells by a factor of five.
In addition, the MVA booster markedly improved the vaccine’s durability, with 100% of recipients continuing to show seropositivity at 6 months, compared with only 50%-74% of participants who did not receive the booster.
The safety profile of the vaccine and the booster were termed “acceptable” at all dose levels and at all dosing intervals studied. There were no serious adverse events, and most adverse events were self-limited and mild. Moderate systemic adverse events included transient fever, myalgia, arthralgia, headache, fatigue, nausea, and malaise. Regarding laboratory abnormalities, four patients showed prolonged activated partial-thromboplastin time without coagulopathy, all of which resolved within 10 weeks; several patients showed mild or moderate lymphocytopenia and mild or moderate elevations in bilirubin, all of which were transient.
Overall, “We found that boosting can be immunogenic for antibodies and T cells at prime-boost intervals as short as 1 week. Such short-interval regimens may facilitate vaccine deployment in outbreak settings where both rapid onset and durable vaccine efficacy are required,” Dr. Ewer and her associates noted (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1411627).
They added that the ChAd3-plus-MVA viral vectors have other practical advantages. “Large-scale manufacturing processes concordant with Good Manufacturing Practice standards have been established, and both vectors have been assessed in large numbers of vaccines for a range of indications, without reports of any substantial safety concerns to date,” Dr. Ewer and her coauthors said.
The second report concerned four parallel studies: three open-label dose-escalation studies in Gabon, Kenya, and Germany and one randomized, double-blind trial in Geneva assessing the safety and immunogenicity of several doses of recombinant vesicular stomatitis virus (rVSV)-vectored ZEBOV. The 158 participants were followed for at least 6 months, said Dr. Selidji T. Agnandji of the Centre de Recherches Medicales de Lambarene (Gabon), the Institut für Tropenmedizin, Universitätsklinikum Tübingen (Germany), and the German Center for Infection Research, Tübingen, and his associates.
The vaccine was immunogenic in all participants across every dose and every study site, with higher glycoprotein-binding antibody titers at higher doses. These antibodies persisted through 6 months, a “promising” result suggesting that a single dose of this vaccine may be sufficient for early and possibly for long-term protection, the investigators said (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1502924).
Although there were no serious adverse events associated with this vaccine, acute vaccine reactions were common: 92% of patients reported an acute reaction, and 10%-22% (depending on the study site) reported grade 3 symptoms. The most bothersome – and unexpected – reactions involved viral seeding of joints and skin.
The joint problems manifested as arthritis, tenosynovitis, or bursitis that appeared at a median of 11 days after injection. The arthritis tended to affect one to four peripheral joints asymmetrically; pain was usually mild and dysfunction was usually moderate. Ten of the 11 affected patients in Geneva and both of the two (out of 60) affected patients at the other sites were symptom-free by 6 months. These findings “suggest a favorable long-term prognosis for these vaccine-induced arthritides,” Dr. Agnandji and his associates said.
Three participants developed maculopapular rashes mainly affecting the limbs, which appeared at 7-9 days following injection and persisted for 1-2 weeks. The rash was accompanied by a few tender vesicles on fingers or toes. Synovial fluid extracted from affected joints and material recovered from skin vesicles showed the presence of rVSV.
Given that most adverse reactions occurred soon after vaccination, were of short duration, and were amenable to treatment, this vaccine demonstrated “a favorable risk-benefit balance,” they added.
Two Ebola vaccines were found safe and effective in separate international phase I trials involving healthy European and African adults, according to two reports published online April 27 in the New England Journal of Medicine.
After further testing and confirmation of these preliminary results, both vaccines should prove useful in both preventing and controlling future outbreaks, both research groups said.
Several vaccines showed promise in previous primate and preliminary human studies, including one expressing the surface glycoprotein of Zaire ebolavirus (ZEBOV). Different versions of this vaccine were assessed in the present phase I studies.
In the first trial, investigators sought to extend the durability of this vaccine by administering a single “priming” dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the ZEBOV surface glycoprotein, then giving a “booster” with a modified vaccinia Ankara (MVA) strain either 1 or 2 weeks later. The participants, 60 healthy adults aged 18-50 years, were randomly assigned to receive a low dose (20 subjects), an intermediate dose (20 subjects), or a high dose (20 subjects) of viral particles. Ten participants from each of these dose groups were then offered the booster. Then two additional groups of eight participants each were assessed to see whether giving the booster at 1 week vs. at 2 weeks made a difference in immunogenicity or safety.
All the study groups showed both antibody and T-cell immunogenicity after vaccination, but the groups that received the boosters showed antibody responses four times higher than those who did not. The MVA booster increased virus-specific antibodies by a factor of 12, and significantly increased neutralizing antibodies as well, said Dr. Katie Ewer of the Jenner Institute and Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford (England) and the National Institute for Health Research Oxford Biomedical Research Centre and her associates.
The boosters also improved the vaccine’s cell-mediated immunity, increasing glycoprotein-specific CD8+ T cells by a factor of five.
In addition, the MVA booster markedly improved the vaccine’s durability, with 100% of recipients continuing to show seropositivity at 6 months, compared with only 50%-74% of participants who did not receive the booster.
The safety profile of the vaccine and the booster were termed “acceptable” at all dose levels and at all dosing intervals studied. There were no serious adverse events, and most adverse events were self-limited and mild. Moderate systemic adverse events included transient fever, myalgia, arthralgia, headache, fatigue, nausea, and malaise. Regarding laboratory abnormalities, four patients showed prolonged activated partial-thromboplastin time without coagulopathy, all of which resolved within 10 weeks; several patients showed mild or moderate lymphocytopenia and mild or moderate elevations in bilirubin, all of which were transient.
Overall, “We found that boosting can be immunogenic for antibodies and T cells at prime-boost intervals as short as 1 week. Such short-interval regimens may facilitate vaccine deployment in outbreak settings where both rapid onset and durable vaccine efficacy are required,” Dr. Ewer and her associates noted (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1411627).
They added that the ChAd3-plus-MVA viral vectors have other practical advantages. “Large-scale manufacturing processes concordant with Good Manufacturing Practice standards have been established, and both vectors have been assessed in large numbers of vaccines for a range of indications, without reports of any substantial safety concerns to date,” Dr. Ewer and her coauthors said.
The second report concerned four parallel studies: three open-label dose-escalation studies in Gabon, Kenya, and Germany and one randomized, double-blind trial in Geneva assessing the safety and immunogenicity of several doses of recombinant vesicular stomatitis virus (rVSV)-vectored ZEBOV. The 158 participants were followed for at least 6 months, said Dr. Selidji T. Agnandji of the Centre de Recherches Medicales de Lambarene (Gabon), the Institut für Tropenmedizin, Universitätsklinikum Tübingen (Germany), and the German Center for Infection Research, Tübingen, and his associates.
The vaccine was immunogenic in all participants across every dose and every study site, with higher glycoprotein-binding antibody titers at higher doses. These antibodies persisted through 6 months, a “promising” result suggesting that a single dose of this vaccine may be sufficient for early and possibly for long-term protection, the investigators said (N Engl J Med. 2016 Apr 27. doi: 10.1056/NEJMoa1502924).
Although there were no serious adverse events associated with this vaccine, acute vaccine reactions were common: 92% of patients reported an acute reaction, and 10%-22% (depending on the study site) reported grade 3 symptoms. The most bothersome – and unexpected – reactions involved viral seeding of joints and skin.
The joint problems manifested as arthritis, tenosynovitis, or bursitis that appeared at a median of 11 days after injection. The arthritis tended to affect one to four peripheral joints asymmetrically; pain was usually mild and dysfunction was usually moderate. Ten of the 11 affected patients in Geneva and both of the two (out of 60) affected patients at the other sites were symptom-free by 6 months. These findings “suggest a favorable long-term prognosis for these vaccine-induced arthritides,” Dr. Agnandji and his associates said.
Three participants developed maculopapular rashes mainly affecting the limbs, which appeared at 7-9 days following injection and persisted for 1-2 weeks. The rash was accompanied by a few tender vesicles on fingers or toes. Synovial fluid extracted from affected joints and material recovered from skin vesicles showed the presence of rVSV.
Given that most adverse reactions occurred soon after vaccination, were of short duration, and were amenable to treatment, this vaccine demonstrated “a favorable risk-benefit balance,” they added.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Two Ebola vaccines were found effective and safe in separate international phase I trials.
Major finding: The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. The rVSV-ZEBOV vaccine was reactogenic but immunogenic after a single dose.
Data source: A single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) was given to 60 healthy adult volunteers in Oxford, England. Three open-label, dose-escalation phase I trials and one randomized, double-blind, controlled phase I trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa.
Disclosures: Dr. Ewer’s study was supported by the Wellcome Trust, the U. K. Medical Research Council, the U. K. Department for International Development, the U. K. National Institute for Health Research Oxford Biomedical Research Centre, the National Health Service Blood and Transplant, and Public Health England. The ChAd3 vaccine was provided by the U.S. Vaccine Research Center of the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline, and the MVA vaccine booster was provided by the NIAID and Fisher BioServices. Dr. Ewer reported having no relevant financial disclosures; some of her associates reported ties to GlaxoSmithKline and patents pending related to these and other vaccines. Dr. Agnandji’s study was supported by the Wellcome Trust, the German Center for Infection Research, the German National Department for Education and Research, the German Ministry of Health, the Bill and Melinda Gates Foundation, Universitätsklinikum Tübingen, the Austrian Federal Ministry of Science, Research, and Economy, and the U.S. Army Medical Research Institute of Infectious Diseases. The rVSV-ZEBOV vaccine used in this study was donated by the Public Health Agency of Canada and the World Health Organization. Dr. Agnandji reported having no relevant financial disclosures; his associates reported ties to Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Sanaria, and Bristol-Myers Squibb.
Sublingual immunotherapy for allergy-related asthma
Immunotherapy using sublingual tablets containing house dust mite allergen extended the interval until patients developed a moderate asthma exacerbation in a manufacturer-sponsored clinical trial reported online April 26 in JAMA.
However, patients’ scores on both the Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire showed no difference between active treatment and placebo. And 25%-27% of the study participants dropped out of the study, usually citing asthma exacerbations, adverse events, or “withdrawal of consent.” Further studies are needed to assess long-term efficacy and safety, said Dr. J. Christian Virchow of the department of pulmonology/intensive care medicine, University of Rostock (Germany), and his associates.
The trial, involving 834 adults with asthma related to house dust mite allergy that was not well controlled by inhaled corticosteroids and short-acting beta-agonists, was performed at 109 sites in 13 European countries during a 2-year period. These participants were randomly assigned to receive add-on daily sublingual tablets containing low-dose dust-mite extract (275 patients), high-dose extract (282 patients), or placebo (277 patients) for 7-12 months. During the final 6 months of the intervention, corticosteroids were reduced by half for 3 months and then withdrawn for 3 months.
The primary efficacy outcome (time to the first asthma exacerbation) was extended by both doses of active drug, compared with placebo, with hazard ratios of 0.69 for the lower dose and 0.66 for the higher dose, the investigators said (JAMA. 2016 Apr 26;315[16]:1715-25).
Adverse events were significantly more frequent with active treatment, affecting 39% of patients receiving the lower dose and 46% of those receiving the higher dose of active immunotherapy, compared with only 17% of patients receiving placebo. However, this study was not adequately powered to compare adverse events across groups, Dr. Virchow and his associates noted.
The most frequently reported adverse events were oral pruritus, mouth edema, and throat irritation, which developed within a median of 1-2 minutes of taking the first dose on day 1 and persisted for a median of 4-23 days. There were 32 serious adverse events, including erosive esophagitis, hepatocellular injury, arthralgia, laryngeal edema, and asthma.
This trial was limited in that treatment duration was much shorter than that for a standard course of immunotherapy, which is often 3 years. This prevents drawing conclusions regarding the sustained effect of the treatment. “Furthermore, because the ultimate aim of allergen immunotherapy is disease modification beyond the duration of treatment, a follow-up after the end of treatment would have been relevant,” the investigators said.
This study was sponsored by the Danish pharmaceutical company ALK. Dr. Virchow reported ties to 31 industry sources; his associates also reported ties to numerous industry sources.
Sublingual immunotherapy appears to be somewhat less effective than subcutaneous immunotherapy, but it offers several advantages. It doesn’t require injections, can be self-administered, doesn’t require dose escalations, and carries a much lower risk of anaphylaxis. However, in this study there were no significant differences in patients’ responses to questionnaires regarding either asthma control or quality of life.
The main disadvantage is that sublingual immunotherapy requires adherence to daily dosing, and research has consistently shown low rates of long-term adherence. In one study, 55%-82% of patients failed to complete the recommended course of sublingual immunotherapy. In another, only 44% of patients renewed their prescriptions after 1 year of treatment, only 28% did so after 2 years, and only 13% did so after 3 years.
Dr. Robert A. Wood is in the division of allergy and immunology, department of pediatrics, at Johns Hopkins University, Baltimore. He reported ties to DBV Technologies, the Immune Tolerance Network, Stallergenes, Sanofi, and UpToDate. Dr. Wood made these remarks in an editorial accompanying Dr. Virchow’s report (JAMA. 2016 Apr 26;315:1711-2).
Sublingual immunotherapy appears to be somewhat less effective than subcutaneous immunotherapy, but it offers several advantages. It doesn’t require injections, can be self-administered, doesn’t require dose escalations, and carries a much lower risk of anaphylaxis. However, in this study there were no significant differences in patients’ responses to questionnaires regarding either asthma control or quality of life.
The main disadvantage is that sublingual immunotherapy requires adherence to daily dosing, and research has consistently shown low rates of long-term adherence. In one study, 55%-82% of patients failed to complete the recommended course of sublingual immunotherapy. In another, only 44% of patients renewed their prescriptions after 1 year of treatment, only 28% did so after 2 years, and only 13% did so after 3 years.
Dr. Robert A. Wood is in the division of allergy and immunology, department of pediatrics, at Johns Hopkins University, Baltimore. He reported ties to DBV Technologies, the Immune Tolerance Network, Stallergenes, Sanofi, and UpToDate. Dr. Wood made these remarks in an editorial accompanying Dr. Virchow’s report (JAMA. 2016 Apr 26;315:1711-2).
Sublingual immunotherapy appears to be somewhat less effective than subcutaneous immunotherapy, but it offers several advantages. It doesn’t require injections, can be self-administered, doesn’t require dose escalations, and carries a much lower risk of anaphylaxis. However, in this study there were no significant differences in patients’ responses to questionnaires regarding either asthma control or quality of life.
The main disadvantage is that sublingual immunotherapy requires adherence to daily dosing, and research has consistently shown low rates of long-term adherence. In one study, 55%-82% of patients failed to complete the recommended course of sublingual immunotherapy. In another, only 44% of patients renewed their prescriptions after 1 year of treatment, only 28% did so after 2 years, and only 13% did so after 3 years.
Dr. Robert A. Wood is in the division of allergy and immunology, department of pediatrics, at Johns Hopkins University, Baltimore. He reported ties to DBV Technologies, the Immune Tolerance Network, Stallergenes, Sanofi, and UpToDate. Dr. Wood made these remarks in an editorial accompanying Dr. Virchow’s report (JAMA. 2016 Apr 26;315:1711-2).
Immunotherapy using sublingual tablets containing house dust mite allergen extended the interval until patients developed a moderate asthma exacerbation in a manufacturer-sponsored clinical trial reported online April 26 in JAMA.
However, patients’ scores on both the Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire showed no difference between active treatment and placebo. And 25%-27% of the study participants dropped out of the study, usually citing asthma exacerbations, adverse events, or “withdrawal of consent.” Further studies are needed to assess long-term efficacy and safety, said Dr. J. Christian Virchow of the department of pulmonology/intensive care medicine, University of Rostock (Germany), and his associates.
The trial, involving 834 adults with asthma related to house dust mite allergy that was not well controlled by inhaled corticosteroids and short-acting beta-agonists, was performed at 109 sites in 13 European countries during a 2-year period. These participants were randomly assigned to receive add-on daily sublingual tablets containing low-dose dust-mite extract (275 patients), high-dose extract (282 patients), or placebo (277 patients) for 7-12 months. During the final 6 months of the intervention, corticosteroids were reduced by half for 3 months and then withdrawn for 3 months.
The primary efficacy outcome (time to the first asthma exacerbation) was extended by both doses of active drug, compared with placebo, with hazard ratios of 0.69 for the lower dose and 0.66 for the higher dose, the investigators said (JAMA. 2016 Apr 26;315[16]:1715-25).
Adverse events were significantly more frequent with active treatment, affecting 39% of patients receiving the lower dose and 46% of those receiving the higher dose of active immunotherapy, compared with only 17% of patients receiving placebo. However, this study was not adequately powered to compare adverse events across groups, Dr. Virchow and his associates noted.
The most frequently reported adverse events were oral pruritus, mouth edema, and throat irritation, which developed within a median of 1-2 minutes of taking the first dose on day 1 and persisted for a median of 4-23 days. There were 32 serious adverse events, including erosive esophagitis, hepatocellular injury, arthralgia, laryngeal edema, and asthma.
This trial was limited in that treatment duration was much shorter than that for a standard course of immunotherapy, which is often 3 years. This prevents drawing conclusions regarding the sustained effect of the treatment. “Furthermore, because the ultimate aim of allergen immunotherapy is disease modification beyond the duration of treatment, a follow-up after the end of treatment would have been relevant,” the investigators said.
This study was sponsored by the Danish pharmaceutical company ALK. Dr. Virchow reported ties to 31 industry sources; his associates also reported ties to numerous industry sources.
Immunotherapy using sublingual tablets containing house dust mite allergen extended the interval until patients developed a moderate asthma exacerbation in a manufacturer-sponsored clinical trial reported online April 26 in JAMA.
However, patients’ scores on both the Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire showed no difference between active treatment and placebo. And 25%-27% of the study participants dropped out of the study, usually citing asthma exacerbations, adverse events, or “withdrawal of consent.” Further studies are needed to assess long-term efficacy and safety, said Dr. J. Christian Virchow of the department of pulmonology/intensive care medicine, University of Rostock (Germany), and his associates.
The trial, involving 834 adults with asthma related to house dust mite allergy that was not well controlled by inhaled corticosteroids and short-acting beta-agonists, was performed at 109 sites in 13 European countries during a 2-year period. These participants were randomly assigned to receive add-on daily sublingual tablets containing low-dose dust-mite extract (275 patients), high-dose extract (282 patients), or placebo (277 patients) for 7-12 months. During the final 6 months of the intervention, corticosteroids were reduced by half for 3 months and then withdrawn for 3 months.
The primary efficacy outcome (time to the first asthma exacerbation) was extended by both doses of active drug, compared with placebo, with hazard ratios of 0.69 for the lower dose and 0.66 for the higher dose, the investigators said (JAMA. 2016 Apr 26;315[16]:1715-25).
Adverse events were significantly more frequent with active treatment, affecting 39% of patients receiving the lower dose and 46% of those receiving the higher dose of active immunotherapy, compared with only 17% of patients receiving placebo. However, this study was not adequately powered to compare adverse events across groups, Dr. Virchow and his associates noted.
The most frequently reported adverse events were oral pruritus, mouth edema, and throat irritation, which developed within a median of 1-2 minutes of taking the first dose on day 1 and persisted for a median of 4-23 days. There were 32 serious adverse events, including erosive esophagitis, hepatocellular injury, arthralgia, laryngeal edema, and asthma.
This trial was limited in that treatment duration was much shorter than that for a standard course of immunotherapy, which is often 3 years. This prevents drawing conclusions regarding the sustained effect of the treatment. “Furthermore, because the ultimate aim of allergen immunotherapy is disease modification beyond the duration of treatment, a follow-up after the end of treatment would have been relevant,” the investigators said.
This study was sponsored by the Danish pharmaceutical company ALK. Dr. Virchow reported ties to 31 industry sources; his associates also reported ties to numerous industry sources.
FROM JAMA
Key clinical point: Sublingual tablets containing house dust mite allergen immunotherapy extended the interval until a moderate or severe asthma exacerbation.
Major finding: The primary efficacy outcome (time to the first asthma exacerbation) was extended by both doses of active drug, compared with placebo, with hazard ratios of 0.69 for the lower dose and 0.66 for the higher dose.
Data source: An industry-sponsored international randomized placebo-controlled trial involving 834 patients.
Disclosures: This study was sponsored by the Danish pharmaceutical company ALK. Dr. Virchow reported ties to 31 industry sources; his associates also reported ties to numerous industry sources.
Isolating asymptomatic C. diff carriers slashes hospital-acquired infections
Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.
In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.
The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.
Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.
During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).
“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.
The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.
Until now, there were no data to determine whether interventions targeting asymptomatic carriers could reduce hospital-acquired C. difficile infection, so these findings are particularly encouraging. But the feasibility of expanding such programs on a larger scale must be carefully considered.
None of the commercially available PCR assays for diagnosing C. difficile has been approved by the Food and Drug Administration for detection in asymptomatic carriers. In addition, screening all patients admitted through the ED is labor and resource intensive, particularly in view of the high cost of PCR assays, and private rooms for isolation may not be available. Moreover, isolation can cause patients anxiety and depression, especially if it is long-term.
Perhaps targeting the highest-risk patients for screening and isolation would be helpful. Patients at high risk for shedding C. difficile spores (such as those who have a history of the infection or who have recently used antibiotics) and patients admitted to high-risk wards such as the ICU may be a good starting point.
Dr. Alice Y. Guh and Dr. L. Clifford McDonald are with the division of healthcare quality promotion at the U.S. Centers for Disease Control and Prevention, Atlanta. They reported having no relevant financial disclosures. Dr. Guh and Dr. McDonald made these remarks in an invited commentary (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.1118) accompanying Dr. Longtin’s report.
Until now, there were no data to determine whether interventions targeting asymptomatic carriers could reduce hospital-acquired C. difficile infection, so these findings are particularly encouraging. But the feasibility of expanding such programs on a larger scale must be carefully considered.
None of the commercially available PCR assays for diagnosing C. difficile has been approved by the Food and Drug Administration for detection in asymptomatic carriers. In addition, screening all patients admitted through the ED is labor and resource intensive, particularly in view of the high cost of PCR assays, and private rooms for isolation may not be available. Moreover, isolation can cause patients anxiety and depression, especially if it is long-term.
Perhaps targeting the highest-risk patients for screening and isolation would be helpful. Patients at high risk for shedding C. difficile spores (such as those who have a history of the infection or who have recently used antibiotics) and patients admitted to high-risk wards such as the ICU may be a good starting point.
Dr. Alice Y. Guh and Dr. L. Clifford McDonald are with the division of healthcare quality promotion at the U.S. Centers for Disease Control and Prevention, Atlanta. They reported having no relevant financial disclosures. Dr. Guh and Dr. McDonald made these remarks in an invited commentary (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.1118) accompanying Dr. Longtin’s report.
Until now, there were no data to determine whether interventions targeting asymptomatic carriers could reduce hospital-acquired C. difficile infection, so these findings are particularly encouraging. But the feasibility of expanding such programs on a larger scale must be carefully considered.
None of the commercially available PCR assays for diagnosing C. difficile has been approved by the Food and Drug Administration for detection in asymptomatic carriers. In addition, screening all patients admitted through the ED is labor and resource intensive, particularly in view of the high cost of PCR assays, and private rooms for isolation may not be available. Moreover, isolation can cause patients anxiety and depression, especially if it is long-term.
Perhaps targeting the highest-risk patients for screening and isolation would be helpful. Patients at high risk for shedding C. difficile spores (such as those who have a history of the infection or who have recently used antibiotics) and patients admitted to high-risk wards such as the ICU may be a good starting point.
Dr. Alice Y. Guh and Dr. L. Clifford McDonald are with the division of healthcare quality promotion at the U.S. Centers for Disease Control and Prevention, Atlanta. They reported having no relevant financial disclosures. Dr. Guh and Dr. McDonald made these remarks in an invited commentary (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.1118) accompanying Dr. Longtin’s report.
Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.
In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.
The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.
Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.
During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).
“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.
The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.
Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.
In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.
The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.
Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.
During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).
“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.
The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Screening asymptomatic patients admitted through the ED for occult C. difficile infection and isolating them throughout their hospital stay substantially reduced the incidence of hospital-acquired C. difficile.
Major finding: 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.
Data source: A controlled quasi-experimental study comparing rates of C. difficile infection at a single hospital during a 1.5-year period before and after an infection-control program was implemented.
Disclosures: This study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.
No Rise in Serious HF Seen in Patients Taking Saxagliptin or Sitagliptin
Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.
The report was published online April 25 in Annals of Internal Medicine.
The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.
They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.
There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.
These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).
However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.
This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.
The findings of Toh et al. allay concerns about a saxagliptin- or sitagliptin-associated risk for heart failure. This risk was similar between the two agents and either comparable to or lower than that in all other comparator groups.
Beyond reassuring clinicians, this study illustrates the value of large, longitudinal databases built from clinical and administrative data, to complement the findings of clinical trials. These investigators were able to draw their conclusions from rich demographic, diagnostic, prescription, and utilization data based in routine real-world practice.
Joseph V. Selby, M.D., is at the Patient-Centered Outcomes Research Institute, Washington. He reported having no relevant financial disclosures. Dr. Selby made these remarks in an editorial accompanying Dr. Toh’s report (Ann. Intern. Med. 2016 April 25. doi:10.7326/M16-0869).
The findings of Toh et al. allay concerns about a saxagliptin- or sitagliptin-associated risk for heart failure. This risk was similar between the two agents and either comparable to or lower than that in all other comparator groups.
Beyond reassuring clinicians, this study illustrates the value of large, longitudinal databases built from clinical and administrative data, to complement the findings of clinical trials. These investigators were able to draw their conclusions from rich demographic, diagnostic, prescription, and utilization data based in routine real-world practice.
Joseph V. Selby, M.D., is at the Patient-Centered Outcomes Research Institute, Washington. He reported having no relevant financial disclosures. Dr. Selby made these remarks in an editorial accompanying Dr. Toh’s report (Ann. Intern. Med. 2016 April 25. doi:10.7326/M16-0869).
The findings of Toh et al. allay concerns about a saxagliptin- or sitagliptin-associated risk for heart failure. This risk was similar between the two agents and either comparable to or lower than that in all other comparator groups.
Beyond reassuring clinicians, this study illustrates the value of large, longitudinal databases built from clinical and administrative data, to complement the findings of clinical trials. These investigators were able to draw their conclusions from rich demographic, diagnostic, prescription, and utilization data based in routine real-world practice.
Joseph V. Selby, M.D., is at the Patient-Centered Outcomes Research Institute, Washington. He reported having no relevant financial disclosures. Dr. Selby made these remarks in an editorial accompanying Dr. Toh’s report (Ann. Intern. Med. 2016 April 25. doi:10.7326/M16-0869).
Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.
The report was published online April 25 in Annals of Internal Medicine.
The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.
They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.
There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.
These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).
However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.
This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.
Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.
The report was published online April 25 in Annals of Internal Medicine.
The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.
They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.
There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.
These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).
However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.
This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.
FROM ANNALS OF INTERNAL MEDICINE
HIV PrEP would help infected drug users, but not cost-effectively
Expanding HIV preexposure prophylaxis to cover people who inject drugs would reduce their disease burden by averting an estimated 26,700 new HIV infections every year, and would also benefit the health of the entire population, according to a cost-effectiveness analysis published online April 25 in Annals of Internal Medicine.
However, such a program would be very expensive, chiefly because of the high current cost of combination tenofovir-emtricitabine therapy, which is approximately $10,000 per patient per year. The overall expense would be higher than is generally considered cost-effective, both in absolute terms and in the cost per quality-adjusted life year (QALY) gained, said Cora L. Bernard of the department of management science and engineering, Stanford (Calif.) University, and her associates.
The investigators used a computer model to analyze the cost-effectiveness of a program offering this segment of the population daily oral tenofovir-emtricitabine plus HIV screening, assessment of adverse effects every 3 months, and antiretroviral treatment (ART) if HIV developed. It assumed that 25% of this group would follow such a program. The model incorporated the results of recent clinical trials along with epidemiologic and economic data such as the incidence of the infection in the approximately 0.56% of the U.S. adult population who use injectable drugs, the effectiveness of prevention programs in such populations, and the costs of treatment according to HIV stage and ART status. The model projected relative benefits and costs over the next 20 years.
Preexposure prophylaxis would prevent an estimated 26,700 new HIV infections among people who use injectable drugs each year, gaining 173,000 QALYs. However, the overall cost over the course of 20 years would be $44 billion, which is the equivalent of spending 10% of the total federal budget for domestic HIV-AIDS on just this small segment of the population. The cost per QALY would be $253,000, well above the generally accepted threshold for cost-effectiveness, the investigators said (Ann Intern Med. 2016 April 25. doi: 10.736/M15-2634).
If the eventual release of a generic version of tenofovir-emtricitabine reduced the price of treatment by 65%, this type of preexposure prophylaxis would cost a projected $100,000 per QALY gained. However, “cost-effectiveness is only one of many considerations for policymakers, who must also evaluate the ethical dimensions of [a national] HIV-prevention program for a population with generally low access to health services,” Ms. Bernard and her associates said.
The National Institute on Drug Abuse, Stanford University, the National Science Foundation, the U.S. Department of Veterans Affairs, and the National Institute on Aging funded the study. Ms. Bernard and her associates reported having no relevant disclosures.
Even if the price of tenofovir, which is anticipated to become generic next year, cuts the cost of HIV preexposure prophylaxis by 65%, and even if this in turn drops the incremental cost-effectiveness ratio of preexposure prophylaxis among drug injectors to $100,000 or less per QALY, the overall price for this kind of program would still be $17 billion over 20 years.
It may be cost-effective, but that doesn’t necessarily mean it is affordable.
Our resources might well be leveraged more effectively. For example, investing in naloxone therapy, detoxification programs, opioid agonist therapy, and needle exchange programs also prevents HIV infection – in some cases, more effectively than preexposure prophylaxis does.
Rochelle P. Walensky, M.D., is at Massachusetts General Hospital, Boston. She made these remarks in an editorial accompanying Ms. Bernard’s report (Ann Intern Med. 2016 April 25. doi: 10.7326/M16-0788).
Even if the price of tenofovir, which is anticipated to become generic next year, cuts the cost of HIV preexposure prophylaxis by 65%, and even if this in turn drops the incremental cost-effectiveness ratio of preexposure prophylaxis among drug injectors to $100,000 or less per QALY, the overall price for this kind of program would still be $17 billion over 20 years.
It may be cost-effective, but that doesn’t necessarily mean it is affordable.
Our resources might well be leveraged more effectively. For example, investing in naloxone therapy, detoxification programs, opioid agonist therapy, and needle exchange programs also prevents HIV infection – in some cases, more effectively than preexposure prophylaxis does.
Rochelle P. Walensky, M.D., is at Massachusetts General Hospital, Boston. She made these remarks in an editorial accompanying Ms. Bernard’s report (Ann Intern Med. 2016 April 25. doi: 10.7326/M16-0788).
Even if the price of tenofovir, which is anticipated to become generic next year, cuts the cost of HIV preexposure prophylaxis by 65%, and even if this in turn drops the incremental cost-effectiveness ratio of preexposure prophylaxis among drug injectors to $100,000 or less per QALY, the overall price for this kind of program would still be $17 billion over 20 years.
It may be cost-effective, but that doesn’t necessarily mean it is affordable.
Our resources might well be leveraged more effectively. For example, investing in naloxone therapy, detoxification programs, opioid agonist therapy, and needle exchange programs also prevents HIV infection – in some cases, more effectively than preexposure prophylaxis does.
Rochelle P. Walensky, M.D., is at Massachusetts General Hospital, Boston. She made these remarks in an editorial accompanying Ms. Bernard’s report (Ann Intern Med. 2016 April 25. doi: 10.7326/M16-0788).
Expanding HIV preexposure prophylaxis to cover people who inject drugs would reduce their disease burden by averting an estimated 26,700 new HIV infections every year, and would also benefit the health of the entire population, according to a cost-effectiveness analysis published online April 25 in Annals of Internal Medicine.
However, such a program would be very expensive, chiefly because of the high current cost of combination tenofovir-emtricitabine therapy, which is approximately $10,000 per patient per year. The overall expense would be higher than is generally considered cost-effective, both in absolute terms and in the cost per quality-adjusted life year (QALY) gained, said Cora L. Bernard of the department of management science and engineering, Stanford (Calif.) University, and her associates.
The investigators used a computer model to analyze the cost-effectiveness of a program offering this segment of the population daily oral tenofovir-emtricitabine plus HIV screening, assessment of adverse effects every 3 months, and antiretroviral treatment (ART) if HIV developed. It assumed that 25% of this group would follow such a program. The model incorporated the results of recent clinical trials along with epidemiologic and economic data such as the incidence of the infection in the approximately 0.56% of the U.S. adult population who use injectable drugs, the effectiveness of prevention programs in such populations, and the costs of treatment according to HIV stage and ART status. The model projected relative benefits and costs over the next 20 years.
Preexposure prophylaxis would prevent an estimated 26,700 new HIV infections among people who use injectable drugs each year, gaining 173,000 QALYs. However, the overall cost over the course of 20 years would be $44 billion, which is the equivalent of spending 10% of the total federal budget for domestic HIV-AIDS on just this small segment of the population. The cost per QALY would be $253,000, well above the generally accepted threshold for cost-effectiveness, the investigators said (Ann Intern Med. 2016 April 25. doi: 10.736/M15-2634).
If the eventual release of a generic version of tenofovir-emtricitabine reduced the price of treatment by 65%, this type of preexposure prophylaxis would cost a projected $100,000 per QALY gained. However, “cost-effectiveness is only one of many considerations for policymakers, who must also evaluate the ethical dimensions of [a national] HIV-prevention program for a population with generally low access to health services,” Ms. Bernard and her associates said.
The National Institute on Drug Abuse, Stanford University, the National Science Foundation, the U.S. Department of Veterans Affairs, and the National Institute on Aging funded the study. Ms. Bernard and her associates reported having no relevant disclosures.
Expanding HIV preexposure prophylaxis to cover people who inject drugs would reduce their disease burden by averting an estimated 26,700 new HIV infections every year, and would also benefit the health of the entire population, according to a cost-effectiveness analysis published online April 25 in Annals of Internal Medicine.
However, such a program would be very expensive, chiefly because of the high current cost of combination tenofovir-emtricitabine therapy, which is approximately $10,000 per patient per year. The overall expense would be higher than is generally considered cost-effective, both in absolute terms and in the cost per quality-adjusted life year (QALY) gained, said Cora L. Bernard of the department of management science and engineering, Stanford (Calif.) University, and her associates.
The investigators used a computer model to analyze the cost-effectiveness of a program offering this segment of the population daily oral tenofovir-emtricitabine plus HIV screening, assessment of adverse effects every 3 months, and antiretroviral treatment (ART) if HIV developed. It assumed that 25% of this group would follow such a program. The model incorporated the results of recent clinical trials along with epidemiologic and economic data such as the incidence of the infection in the approximately 0.56% of the U.S. adult population who use injectable drugs, the effectiveness of prevention programs in such populations, and the costs of treatment according to HIV stage and ART status. The model projected relative benefits and costs over the next 20 years.
Preexposure prophylaxis would prevent an estimated 26,700 new HIV infections among people who use injectable drugs each year, gaining 173,000 QALYs. However, the overall cost over the course of 20 years would be $44 billion, which is the equivalent of spending 10% of the total federal budget for domestic HIV-AIDS on just this small segment of the population. The cost per QALY would be $253,000, well above the generally accepted threshold for cost-effectiveness, the investigators said (Ann Intern Med. 2016 April 25. doi: 10.736/M15-2634).
If the eventual release of a generic version of tenofovir-emtricitabine reduced the price of treatment by 65%, this type of preexposure prophylaxis would cost a projected $100,000 per QALY gained. However, “cost-effectiveness is only one of many considerations for policymakers, who must also evaluate the ethical dimensions of [a national] HIV-prevention program for a population with generally low access to health services,” Ms. Bernard and her associates said.
The National Institute on Drug Abuse, Stanford University, the National Science Foundation, the U.S. Department of Veterans Affairs, and the National Institute on Aging funded the study. Ms. Bernard and her associates reported having no relevant disclosures.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: HIV preexposure prophylaxis for people who inject drugs would reduce their disease burden by averting 26,700 new HIV infections each year and would benefit the health of the entire population.
Major finding: Preexposure prophylaxis would gain 173,000 QALYs each year among people who inject drugs, at a cost of $253,000 per QALY.
Data source: A cost-effectiveness analysis of expanding preexposure prophylaxis to the approximately 0.6% of the adult U.S. population who inject drugs.
Disclosures: The National Institute on Drug Abuse, Stanford University, the National Science Foundation, the U.S. Department of Veterans Affairs, and the National Institute on Aging funded the study. Ms. Bernard and her associates reported having no relevant disclosures.
CML: T3151 plus additional mutations predicts poor response to ponatinib
Depending on the number and type of BCR-ABL1 mutations, certain patients with chronic myeloid leukemia may have a better response to ponatinib than to other tyrosine kinase inhibitors, according to a report published in Blood.
For patients with CML treated with first- or second-generation tyrosine kinase inhibitors such as imatinib, nilotinib, and dasatinib, the most common cause of treatment failure is the acquisition of mutations in the BCR-ABL1 gene, particularly the T315I mutation, which interfere with drug binding and eventually confer drug resistance. Some of these cancers have proved susceptible to ponatinib, but treatment response varies among patients, said Dr. Wendy T. Parker of the Australian Cancer Research Foundation (ACRF) Cancer Genomics Facility, the Center for Cancer Biology, and the University of Adelaide (Australia) and her associates.
They retrospectively assessed peripheral blood samples from 363 CML patients who had taken part in a phase II study of ponatinib therapy, using their newly developed mass spectrometry–based mutation detection assay to determine which mutations correlated with which treatment outcomes. These study participants contributed blood samples before, during, and after ponatinib treatment. The mass spectrometry–based assay can detect BCR-ABL1 KD mutations present at levels between 10- and 100-fold below those detectable using conventional Sanger sequencing, the researchers said (Blood. 2016;127[15]:1870-80).
Patients who had the T315I mutation plus additional mutations at baseline (32% of the study population) had significantly worse treatment responses and significantly worse outcomes than those who had only the T315I mutation at baseline. “Consequently, these patients may benefit from close monitoring, experimental approaches, or stem-cell transplantation to reduce the risk of tyrosine kinase inhibitor failure,” Dr. Parker and her associates said.
In addition, patients who didn’t have the T315I mutation but had multiple other mutations at baseline responded well to ponatinib. Historically, such patients have not responded well to first- or second-generation tyrosine kinase inhibitors, but ponatinib may prove to be a particularly effective option for this patient population, the investigators said (Blood. 2016;127[15]:1870-80).
These findings demonstrate that mutation analysis, such as that provided by their mass spectrometry–based assay, can be used to guide therapy even after patients have failed on some tyrosine kinase inhibitors, they added.
The study was supported by the maker of ponatinib (Iclusig) Ariad Pharmaceuticals, the Leukemia Foundation of Australia, and the A.R. Clarkson Foundation. Dr. Parker reported having no relevant financial disclosures; some of her associates were employed by Ariad.
Depending on the number and type of BCR-ABL1 mutations, certain patients with chronic myeloid leukemia may have a better response to ponatinib than to other tyrosine kinase inhibitors, according to a report published in Blood.
For patients with CML treated with first- or second-generation tyrosine kinase inhibitors such as imatinib, nilotinib, and dasatinib, the most common cause of treatment failure is the acquisition of mutations in the BCR-ABL1 gene, particularly the T315I mutation, which interfere with drug binding and eventually confer drug resistance. Some of these cancers have proved susceptible to ponatinib, but treatment response varies among patients, said Dr. Wendy T. Parker of the Australian Cancer Research Foundation (ACRF) Cancer Genomics Facility, the Center for Cancer Biology, and the University of Adelaide (Australia) and her associates.
They retrospectively assessed peripheral blood samples from 363 CML patients who had taken part in a phase II study of ponatinib therapy, using their newly developed mass spectrometry–based mutation detection assay to determine which mutations correlated with which treatment outcomes. These study participants contributed blood samples before, during, and after ponatinib treatment. The mass spectrometry–based assay can detect BCR-ABL1 KD mutations present at levels between 10- and 100-fold below those detectable using conventional Sanger sequencing, the researchers said (Blood. 2016;127[15]:1870-80).
Patients who had the T315I mutation plus additional mutations at baseline (32% of the study population) had significantly worse treatment responses and significantly worse outcomes than those who had only the T315I mutation at baseline. “Consequently, these patients may benefit from close monitoring, experimental approaches, or stem-cell transplantation to reduce the risk of tyrosine kinase inhibitor failure,” Dr. Parker and her associates said.
In addition, patients who didn’t have the T315I mutation but had multiple other mutations at baseline responded well to ponatinib. Historically, such patients have not responded well to first- or second-generation tyrosine kinase inhibitors, but ponatinib may prove to be a particularly effective option for this patient population, the investigators said (Blood. 2016;127[15]:1870-80).
These findings demonstrate that mutation analysis, such as that provided by their mass spectrometry–based assay, can be used to guide therapy even after patients have failed on some tyrosine kinase inhibitors, they added.
The study was supported by the maker of ponatinib (Iclusig) Ariad Pharmaceuticals, the Leukemia Foundation of Australia, and the A.R. Clarkson Foundation. Dr. Parker reported having no relevant financial disclosures; some of her associates were employed by Ariad.
Depending on the number and type of BCR-ABL1 mutations, certain patients with chronic myeloid leukemia may have a better response to ponatinib than to other tyrosine kinase inhibitors, according to a report published in Blood.
For patients with CML treated with first- or second-generation tyrosine kinase inhibitors such as imatinib, nilotinib, and dasatinib, the most common cause of treatment failure is the acquisition of mutations in the BCR-ABL1 gene, particularly the T315I mutation, which interfere with drug binding and eventually confer drug resistance. Some of these cancers have proved susceptible to ponatinib, but treatment response varies among patients, said Dr. Wendy T. Parker of the Australian Cancer Research Foundation (ACRF) Cancer Genomics Facility, the Center for Cancer Biology, and the University of Adelaide (Australia) and her associates.
They retrospectively assessed peripheral blood samples from 363 CML patients who had taken part in a phase II study of ponatinib therapy, using their newly developed mass spectrometry–based mutation detection assay to determine which mutations correlated with which treatment outcomes. These study participants contributed blood samples before, during, and after ponatinib treatment. The mass spectrometry–based assay can detect BCR-ABL1 KD mutations present at levels between 10- and 100-fold below those detectable using conventional Sanger sequencing, the researchers said (Blood. 2016;127[15]:1870-80).
Patients who had the T315I mutation plus additional mutations at baseline (32% of the study population) had significantly worse treatment responses and significantly worse outcomes than those who had only the T315I mutation at baseline. “Consequently, these patients may benefit from close monitoring, experimental approaches, or stem-cell transplantation to reduce the risk of tyrosine kinase inhibitor failure,” Dr. Parker and her associates said.
In addition, patients who didn’t have the T315I mutation but had multiple other mutations at baseline responded well to ponatinib. Historically, such patients have not responded well to first- or second-generation tyrosine kinase inhibitors, but ponatinib may prove to be a particularly effective option for this patient population, the investigators said (Blood. 2016;127[15]:1870-80).
These findings demonstrate that mutation analysis, such as that provided by their mass spectrometry–based assay, can be used to guide therapy even after patients have failed on some tyrosine kinase inhibitors, they added.
The study was supported by the maker of ponatinib (Iclusig) Ariad Pharmaceuticals, the Leukemia Foundation of Australia, and the A.R. Clarkson Foundation. Dr. Parker reported having no relevant financial disclosures; some of her associates were employed by Ariad.
FROM BLOOD
Key clinical point: The third-generation tyrosine kinase inhibitor ponatinib appears to be more effective than its predecessors against certain cases of chronic myeloid leukemia defined by the number and type of BCR-ABL1 mutations that patients have.
Major finding: Patients who had the T315I mutation plus additional mutations at baseline (32% of the study population) had significantly worse treatment responses and outcomes than those who had only the T315I mutation and those who had multiple other mutations.
Data source: A retrospective secondary analysis of data from a phase II clinical trial involving 363 patients with CML.
Disclosures: This study was supported by the maker of ponatinib (Iclusig) Ariad Pharmaceuticals, the Leukemia Foundation of Australia, and the A.R. Clarkson Foundation. Dr. Parker reported having no relevant financial disclosures; some of her associates were employed by Ariad.