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Wait at least 2 days to replace central venous catheters in patients with candidemia
SAN DIEGO – Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.
Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”
Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.
Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).
Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.
Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.
The researchers reported having no conflicts of interest.
SAN DIEGO – Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.
Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”
Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.
Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).
Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.
Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.
The researchers reported having no conflicts of interest.
SAN DIEGO – Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.
Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”
Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.
Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).
Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.
Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.
The researchers reported having no conflicts of interest.
AT IDWEEK 2017
Key clinical point: Consider waiting at least 2 days to replace a central venous catheter that has been removed because of candidemia.
Major finding: (odds ratio, 5.9; 95% confidence interval, 1.2-27.3).
Data source: A single-center retrospective cohort study of 228 patients with candidemia.
Disclosures: The researchers reported having no conflicts of interest.
A game of telephone?
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
The transfer of information from floor to the MICU team is a very interesting process: outside of the patient record, the person performing the handoff is highly responsible in the appropriate transfer of information.
One of the challenges encountered within the project is the way in which we are categorizing agreement between groups. Previously, we created a set of categories based upon recurring themes present within the free-text provider responses, and created categories, such as “cardiac management” and “diabetes management.” Upon creating these categories, I would then group them based upon concordance. However, responses such as “bipap during the night” and “not giving her bipap” would both be coded under “respiratory management,” but those two responses would not show the providers being in concordance. Upon consulting with my mentors Dr. Vineet Arora and Dr. Juan Rojas, we decided that it would be more accurate to categorize concordance based upon the original answers, keeping the breadth of the original data intact.
As I continue to organize the data based on concordance, I have to modify my frame of thought and focus on appropriately representing the responses. There is no such thing as perfect data, and this project is no exception; in this case, not every provider was able to be reached for a response, which requires more nuance as I categorize the degree of concordance within the data and think of appropriate categories. I am very glad to learn the skill of appropriate data representation, as we want it to demonstrate both the potential lack or presence of clarity in handoffs, as well as the represented responding providers.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago. He received his bachelor of science degree in biology from Loyola University in Chicago in 2015 and his master of biomedical science degree from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
The transfer of information from floor to the MICU team is a very interesting process: outside of the patient record, the person performing the handoff is highly responsible in the appropriate transfer of information.
One of the challenges encountered within the project is the way in which we are categorizing agreement between groups. Previously, we created a set of categories based upon recurring themes present within the free-text provider responses, and created categories, such as “cardiac management” and “diabetes management.” Upon creating these categories, I would then group them based upon concordance. However, responses such as “bipap during the night” and “not giving her bipap” would both be coded under “respiratory management,” but those two responses would not show the providers being in concordance. Upon consulting with my mentors Dr. Vineet Arora and Dr. Juan Rojas, we decided that it would be more accurate to categorize concordance based upon the original answers, keeping the breadth of the original data intact.
As I continue to organize the data based on concordance, I have to modify my frame of thought and focus on appropriately representing the responses. There is no such thing as perfect data, and this project is no exception; in this case, not every provider was able to be reached for a response, which requires more nuance as I categorize the degree of concordance within the data and think of appropriate categories. I am very glad to learn the skill of appropriate data representation, as we want it to demonstrate both the potential lack or presence of clarity in handoffs, as well as the represented responding providers.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago. He received his bachelor of science degree in biology from Loyola University in Chicago in 2015 and his master of biomedical science degree from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform healthcare and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
The transfer of information from floor to the MICU team is a very interesting process: outside of the patient record, the person performing the handoff is highly responsible in the appropriate transfer of information.
One of the challenges encountered within the project is the way in which we are categorizing agreement between groups. Previously, we created a set of categories based upon recurring themes present within the free-text provider responses, and created categories, such as “cardiac management” and “diabetes management.” Upon creating these categories, I would then group them based upon concordance. However, responses such as “bipap during the night” and “not giving her bipap” would both be coded under “respiratory management,” but those two responses would not show the providers being in concordance. Upon consulting with my mentors Dr. Vineet Arora and Dr. Juan Rojas, we decided that it would be more accurate to categorize concordance based upon the original answers, keeping the breadth of the original data intact.
As I continue to organize the data based on concordance, I have to modify my frame of thought and focus on appropriately representing the responses. There is no such thing as perfect data, and this project is no exception; in this case, not every provider was able to be reached for a response, which requires more nuance as I categorize the degree of concordance within the data and think of appropriate categories. I am very glad to learn the skill of appropriate data representation, as we want it to demonstrate both the potential lack or presence of clarity in handoffs, as well as the represented responding providers.
Anton Garazha is a medical student at Chicago Medical School at Rosalind Franklin University in North Chicago. He received his bachelor of science degree in biology from Loyola University in Chicago in 2015 and his master of biomedical science degree from Rosalind Franklin University in 2016. Anton is very interested in community outreach and quality improvement, and in his spare time tutors students in science-based subjects.
Thinking about the basic science of quality improvement
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
I reviewed recent literature about my research topic, which is clinical pathways for hospitalized injection drug users due to injection-related infection sequelae and came up with my research proposal. As part of a scholarly pursuit, I believe having a theoretical background of quality improvement to be important. Before further diving into the research topic, I also generated a small reading list of the “basic science” of quality improvement, which covers topics of general operational science and those in health care applications.
What makes standardization in health care difficult? In my operations class at Tuck School of Business, we watched a video showing former Soviet Union ophthalmologists performing “assembly line” cataract surgery. It includes multiple surgeons sitting around multiple rotating tables, each surgeon performing exactly one step of the cataract surgery. I recall all my classmates were amused by the video, because it appeared both impractical (as one surgeon was almost chasing the table) as well as slightly de-humanizing. In the health care setting, standardization can be difficult. The service is intrinsically complex, it is difficult to define processes and to measure outcomes, and standardization can create tension secondary to physician autonomy and organizational culture.
In service delivery, the person (the patient in health care organizations) is part of the production process. Patients by nature are not standard inputs. They assume different pre-existing conditions and have different preferences for clinical and non-clinical services/processes. The medical service itself, consisting of both clinical and operational processes, sometimes can be difficult to qualify and measure. A hospital can control patient flow by managing appointment and beds allocation. Clinical pathways can be defined for different diseases. However, patients can encounter undiscovered diseases or complications during the treatment, making the clinical service different and unpredictable.
Lastly standardization can encounter resistance from physicians and other health care providers. “Patients are not cars” is a phrase commonly used when discussing standardization. A health care organization needs to have not only tools, but also the cultural and managerial foundations to carry out changes. I am looking forward to using this project opportunity to further explore the local application of quality improvement.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
I reviewed recent literature about my research topic, which is clinical pathways for hospitalized injection drug users due to injection-related infection sequelae and came up with my research proposal. As part of a scholarly pursuit, I believe having a theoretical background of quality improvement to be important. Before further diving into the research topic, I also generated a small reading list of the “basic science” of quality improvement, which covers topics of general operational science and those in health care applications.
What makes standardization in health care difficult? In my operations class at Tuck School of Business, we watched a video showing former Soviet Union ophthalmologists performing “assembly line” cataract surgery. It includes multiple surgeons sitting around multiple rotating tables, each surgeon performing exactly one step of the cataract surgery. I recall all my classmates were amused by the video, because it appeared both impractical (as one surgeon was almost chasing the table) as well as slightly de-humanizing. In the health care setting, standardization can be difficult. The service is intrinsically complex, it is difficult to define processes and to measure outcomes, and standardization can create tension secondary to physician autonomy and organizational culture.
In service delivery, the person (the patient in health care organizations) is part of the production process. Patients by nature are not standard inputs. They assume different pre-existing conditions and have different preferences for clinical and non-clinical services/processes. The medical service itself, consisting of both clinical and operational processes, sometimes can be difficult to qualify and measure. A hospital can control patient flow by managing appointment and beds allocation. Clinical pathways can be defined for different diseases. However, patients can encounter undiscovered diseases or complications during the treatment, making the clinical service different and unpredictable.
Lastly standardization can encounter resistance from physicians and other health care providers. “Patients are not cars” is a phrase commonly used when discussing standardization. A health care organization needs to have not only tools, but also the cultural and managerial foundations to carry out changes. I am looking forward to using this project opportunity to further explore the local application of quality improvement.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
I reviewed recent literature about my research topic, which is clinical pathways for hospitalized injection drug users due to injection-related infection sequelae and came up with my research proposal. As part of a scholarly pursuit, I believe having a theoretical background of quality improvement to be important. Before further diving into the research topic, I also generated a small reading list of the “basic science” of quality improvement, which covers topics of general operational science and those in health care applications.
What makes standardization in health care difficult? In my operations class at Tuck School of Business, we watched a video showing former Soviet Union ophthalmologists performing “assembly line” cataract surgery. It includes multiple surgeons sitting around multiple rotating tables, each surgeon performing exactly one step of the cataract surgery. I recall all my classmates were amused by the video, because it appeared both impractical (as one surgeon was almost chasing the table) as well as slightly de-humanizing. In the health care setting, standardization can be difficult. The service is intrinsically complex, it is difficult to define processes and to measure outcomes, and standardization can create tension secondary to physician autonomy and organizational culture.
In service delivery, the person (the patient in health care organizations) is part of the production process. Patients by nature are not standard inputs. They assume different pre-existing conditions and have different preferences for clinical and non-clinical services/processes. The medical service itself, consisting of both clinical and operational processes, sometimes can be difficult to qualify and measure. A hospital can control patient flow by managing appointment and beds allocation. Clinical pathways can be defined for different diseases. However, patients can encounter undiscovered diseases or complications during the treatment, making the clinical service different and unpredictable.
Lastly standardization can encounter resistance from physicians and other health care providers. “Patients are not cars” is a phrase commonly used when discussing standardization. A health care organization needs to have not only tools, but also the cultural and managerial foundations to carry out changes. I am looking forward to using this project opportunity to further explore the local application of quality improvement.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Everolimus has long-term efficacy in tuberous sclerosis complex
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
AT ANA 2017
Key clinical point:
Major finding: The response rate rose from 31% at week 18 to 57.7% at 2 years.
Data source: An extension study of a double-blind, randomized, placebo-controlled trial (n = 361).
Disclosures: The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
Slow-wave sleep linked to Parkinson’s disease cognition
SAN DIEGO – Slow-wave sleep improves cognition in Parkinson’s disease, according to University of Alabama at Birmingham investigators.
After sleep studies, they compared the cognitive performance of 16 patients who spent more than 14% of their sleep time in slow-wave (SW) sleep with the cognitive performance of 16 who spent less than 14% in SW sleep; 13 of the patients in the low SW group (81%) met the criteria for mild Parkinson’s disease (PD) cognitive impairment versus 7 of the patients in the higher SW sleep group (44%); the patients were well matched for age, sex, disease duration, and other variables.
The normative value for SW sleep is about 15%-20%, although people spend less time in SW sleep as they age. The study subjects were in their mid-60s on average, so the 14% cut point wasn’t too far off from what might be considered typical.
More SW sleep in PD was associated with better performance on measures of global function, attention/working memory, executive function, and language comprehension. Patients in the low SW group, for instance, performed 0.25 standard deviations below the normative mean on attention/working memory tests, while subjects in the high SW group performed 0.5 standard deviations above, meaning that they outperformed people in their age group who didn’t have PD. These differences were statistically significant.
It raises the question of what can be done to help PD patients sleep better. “I’m interested in exercise to improve sleep, and we have some primary data that show it’s helpful for sleep in general but also SW sleep,” said Dr. Amara. Sodium oxybate (Xyrem) might also help, but for now, it’s a controlled substance approved only for narcolepsy. “We might have to branch out and try something novel,” she said. 
The next step is to “see if we can use SW sleep to predict who might have cognitive declines and find interventions to [prevent] it,” she said.
Patients in the study had been diagnosed with PD for a mean of about 7 years. People in the high SW group were on lower amounts of levodopa equivalents, however, the investigators controlled for that, as well as for the fact that women tend to spend more time in SW sleep than men. There were no differences between the groups in measures of movement problems and of subjective scores of sleep quality and daytime sleepiness.
People with high SW sleep fell asleep sooner than did those in the low SW groups, about 9 minutes versus 20 minutes. There was no correlation between visual-spatial function and SW sleep, but visual-spatial function did correlate with the amount of time spent in rapid eye movement sleep, suggesting that dreaming might be important for visual-spatial function, Dr. Amara said.
The work was funded by the National Institutes of Health. Dr. Amara had no relevant disclosures.
SAN DIEGO – Slow-wave sleep improves cognition in Parkinson’s disease, according to University of Alabama at Birmingham investigators.
After sleep studies, they compared the cognitive performance of 16 patients who spent more than 14% of their sleep time in slow-wave (SW) sleep with the cognitive performance of 16 who spent less than 14% in SW sleep; 13 of the patients in the low SW group (81%) met the criteria for mild Parkinson’s disease (PD) cognitive impairment versus 7 of the patients in the higher SW sleep group (44%); the patients were well matched for age, sex, disease duration, and other variables.
The normative value for SW sleep is about 15%-20%, although people spend less time in SW sleep as they age. The study subjects were in their mid-60s on average, so the 14% cut point wasn’t too far off from what might be considered typical.
More SW sleep in PD was associated with better performance on measures of global function, attention/working memory, executive function, and language comprehension. Patients in the low SW group, for instance, performed 0.25 standard deviations below the normative mean on attention/working memory tests, while subjects in the high SW group performed 0.5 standard deviations above, meaning that they outperformed people in their age group who didn’t have PD. These differences were statistically significant.
It raises the question of what can be done to help PD patients sleep better. “I’m interested in exercise to improve sleep, and we have some primary data that show it’s helpful for sleep in general but also SW sleep,” said Dr. Amara. Sodium oxybate (Xyrem) might also help, but for now, it’s a controlled substance approved only for narcolepsy. “We might have to branch out and try something novel,” she said.
The next step is to “see if we can use SW sleep to predict who might have cognitive declines and find interventions to [prevent] it,” she said.
Patients in the study had been diagnosed with PD for a mean of about 7 years. People in the high SW group were on lower amounts of levodopa equivalents, however, the investigators controlled for that, as well as for the fact that women tend to spend more time in SW sleep than men. There were no differences between the groups in measures of movement problems and of subjective scores of sleep quality and daytime sleepiness.
People with high SW sleep fell asleep sooner than did those in the low SW groups, about 9 minutes versus 20 minutes. There was no correlation between visual-spatial function and SW sleep, but visual-spatial function did correlate with the amount of time spent in rapid eye movement sleep, suggesting that dreaming might be important for visual-spatial function, Dr. Amara said.
The work was funded by the National Institutes of Health. Dr. Amara had no relevant disclosures.
SAN DIEGO – Slow-wave sleep improves cognition in Parkinson’s disease, according to University of Alabama at Birmingham investigators.
After sleep studies, they compared the cognitive performance of 16 patients who spent more than 14% of their sleep time in slow-wave (SW) sleep with the cognitive performance of 16 who spent less than 14% in SW sleep; 13 of the patients in the low SW group (81%) met the criteria for mild Parkinson’s disease (PD) cognitive impairment versus 7 of the patients in the higher SW sleep group (44%); the patients were well matched for age, sex, disease duration, and other variables.
The normative value for SW sleep is about 15%-20%, although people spend less time in SW sleep as they age. The study subjects were in their mid-60s on average, so the 14% cut point wasn’t too far off from what might be considered typical.
More SW sleep in PD was associated with better performance on measures of global function, attention/working memory, executive function, and language comprehension. Patients in the low SW group, for instance, performed 0.25 standard deviations below the normative mean on attention/working memory tests, while subjects in the high SW group performed 0.5 standard deviations above, meaning that they outperformed people in their age group who didn’t have PD. These differences were statistically significant.
It raises the question of what can be done to help PD patients sleep better. “I’m interested in exercise to improve sleep, and we have some primary data that show it’s helpful for sleep in general but also SW sleep,” said Dr. Amara. Sodium oxybate (Xyrem) might also help, but for now, it’s a controlled substance approved only for narcolepsy. “We might have to branch out and try something novel,” she said.
The next step is to “see if we can use SW sleep to predict who might have cognitive declines and find interventions to [prevent] it,” she said.
Patients in the study had been diagnosed with PD for a mean of about 7 years. People in the high SW group were on lower amounts of levodopa equivalents, however, the investigators controlled for that, as well as for the fact that women tend to spend more time in SW sleep than men. There were no differences between the groups in measures of movement problems and of subjective scores of sleep quality and daytime sleepiness.
People with high SW sleep fell asleep sooner than did those in the low SW groups, about 9 minutes versus 20 minutes. There was no correlation between visual-spatial function and SW sleep, but visual-spatial function did correlate with the amount of time spent in rapid eye movement sleep, suggesting that dreaming might be important for visual-spatial function, Dr. Amara said.
The work was funded by the National Institutes of Health. Dr. Amara had no relevant disclosures.
AT ANA 2017
Key clinical point:
Major finding: Thirteen patients in the low SW group (81%) met criteria for mild Parkinson’s disease (PD) cognitive impairment versus seven (44%) in the higher SW sleep group.
Data source: Cognitive testing of 32 patients with PD stratified by amount of SW sleep
Disclosures: The work was funded by the National Institutes of Health. The presenter had no relevant disclosures.
Post-Ebola syndrome includes neurologic sequelae
SAN DIEGO – Add neurologic issues to the growing list of medical problems faced by survivors of Ebola virus.
Among 153 Liberian patients about a year out from their acute illness, “there were only a handful who didn’t have” some lingering neurologic problem. “The most commonly reported ongoing symptoms were headache and memory loss. A couple of people had seizures possibly related to Ebola.” Depression, anxiety, and posttraumatic stress disorder were common, said neurologist Jeanne Billioux, MD, a clinical fellow at the National Institute of Neurological Disorders and Stroke, Bethesda, Md.
Almost two-thirds of the patients had abnormal neurologic exams. The most common findings were tremors, pathological reflexes, mild dysmetria, and abnormalities of eye pursuits and saccades, plus nystagmus. The findings were statistically significant, compared with 81 close contacts, generally household members, who served as controls in the ongoing natural history study, which was presented at the annual meeting of the American Neurological Association.
What’s become clear in the wake of the recent outbreak in West Africa, by far the worst to date with over 28,000 cases and more than 11,000 deaths, is that there is a post-Ebola syndrome that includes ophthalmologic, cardiac, and rheumatologic problems. It now appears that “neurologic sequelae are a part of it,” as well, she said.
The natural history study – dubbed the Partnership for Research on Ebola Virus in Liberia (PREVAIL III) – is a collaboration between the National Institutes of Health and the Ministry of Health of Liberia, one of the hardest-hit countries; the neurology investigation is just one component of the study, which includes about 1,500 patients overall.
Serology testing confirmed that cases truly did have Ebola, and the controls did not. After the first evaluation a year or so after the acute illness, patients have been followed up every 6 months, with some out to about 3 years.
Although patients aren’t back to normal, the good news is that their symptoms and exams are improving. “We started with only 6 who had no symptoms; now we have 15. Headaches are getting better; memory is getting better. It’s wonderful,” Dr. Billioux said.
The patients were asked to recall their acute symptoms during their first study visit. Many reported headaches, weakness, altered mental status, and cranial nerve symptoms. About 2% described convulsions or strokelike symptoms, and about 25% described symptoms consistent with meningitis.
It’s unclear how the virus affected the CNS, which isn’t considered to be a target organ. Perhaps fluid loss from severe diarrhea led to cerebral hypoperfusion. The cytokine storm during the acute phase might also have played a role. The virus has, however, been isolated from cerebral spinal fluid and, although uncommon, there are the reports of meningitis symptoms, so perhaps it does have direct CNS effects. Much remains to be learned.
Both cases and controls were a mean of about 35 years old, and evenly split between the sexes; 108 patients (70.6%) spent more than 2 weeks in an Ebola treatment unit.
The work was funded by the National Institutes of Health. Dr. Billioux had no disclosures.
SAN DIEGO – Add neurologic issues to the growing list of medical problems faced by survivors of Ebola virus.
Among 153 Liberian patients about a year out from their acute illness, “there were only a handful who didn’t have” some lingering neurologic problem. “The most commonly reported ongoing symptoms were headache and memory loss. A couple of people had seizures possibly related to Ebola.” Depression, anxiety, and posttraumatic stress disorder were common, said neurologist Jeanne Billioux, MD, a clinical fellow at the National Institute of Neurological Disorders and Stroke, Bethesda, Md.
Almost two-thirds of the patients had abnormal neurologic exams. The most common findings were tremors, pathological reflexes, mild dysmetria, and abnormalities of eye pursuits and saccades, plus nystagmus. The findings were statistically significant, compared with 81 close contacts, generally household members, who served as controls in the ongoing natural history study, which was presented at the annual meeting of the American Neurological Association.
What’s become clear in the wake of the recent outbreak in West Africa, by far the worst to date with over 28,000 cases and more than 11,000 deaths, is that there is a post-Ebola syndrome that includes ophthalmologic, cardiac, and rheumatologic problems. It now appears that “neurologic sequelae are a part of it,” as well, she said.
The natural history study – dubbed the Partnership for Research on Ebola Virus in Liberia (PREVAIL III) – is a collaboration between the National Institutes of Health and the Ministry of Health of Liberia, one of the hardest-hit countries; the neurology investigation is just one component of the study, which includes about 1,500 patients overall.
Serology testing confirmed that cases truly did have Ebola, and the controls did not. After the first evaluation a year or so after the acute illness, patients have been followed up every 6 months, with some out to about 3 years.
Although patients aren’t back to normal, the good news is that their symptoms and exams are improving. “We started with only 6 who had no symptoms; now we have 15. Headaches are getting better; memory is getting better. It’s wonderful,” Dr. Billioux said.
The patients were asked to recall their acute symptoms during their first study visit. Many reported headaches, weakness, altered mental status, and cranial nerve symptoms. About 2% described convulsions or strokelike symptoms, and about 25% described symptoms consistent with meningitis.
It’s unclear how the virus affected the CNS, which isn’t considered to be a target organ. Perhaps fluid loss from severe diarrhea led to cerebral hypoperfusion. The cytokine storm during the acute phase might also have played a role. The virus has, however, been isolated from cerebral spinal fluid and, although uncommon, there are the reports of meningitis symptoms, so perhaps it does have direct CNS effects. Much remains to be learned.
Both cases and controls were a mean of about 35 years old, and evenly split between the sexes; 108 patients (70.6%) spent more than 2 weeks in an Ebola treatment unit.
The work was funded by the National Institutes of Health. Dr. Billioux had no disclosures.
SAN DIEGO – Add neurologic issues to the growing list of medical problems faced by survivors of Ebola virus.
Among 153 Liberian patients about a year out from their acute illness, “there were only a handful who didn’t have” some lingering neurologic problem. “The most commonly reported ongoing symptoms were headache and memory loss. A couple of people had seizures possibly related to Ebola.” Depression, anxiety, and posttraumatic stress disorder were common, said neurologist Jeanne Billioux, MD, a clinical fellow at the National Institute of Neurological Disorders and Stroke, Bethesda, Md.
Almost two-thirds of the patients had abnormal neurologic exams. The most common findings were tremors, pathological reflexes, mild dysmetria, and abnormalities of eye pursuits and saccades, plus nystagmus. The findings were statistically significant, compared with 81 close contacts, generally household members, who served as controls in the ongoing natural history study, which was presented at the annual meeting of the American Neurological Association.
What’s become clear in the wake of the recent outbreak in West Africa, by far the worst to date with over 28,000 cases and more than 11,000 deaths, is that there is a post-Ebola syndrome that includes ophthalmologic, cardiac, and rheumatologic problems. It now appears that “neurologic sequelae are a part of it,” as well, she said.
The natural history study – dubbed the Partnership for Research on Ebola Virus in Liberia (PREVAIL III) – is a collaboration between the National Institutes of Health and the Ministry of Health of Liberia, one of the hardest-hit countries; the neurology investigation is just one component of the study, which includes about 1,500 patients overall.
Serology testing confirmed that cases truly did have Ebola, and the controls did not. After the first evaluation a year or so after the acute illness, patients have been followed up every 6 months, with some out to about 3 years.
Although patients aren’t back to normal, the good news is that their symptoms and exams are improving. “We started with only 6 who had no symptoms; now we have 15. Headaches are getting better; memory is getting better. It’s wonderful,” Dr. Billioux said.
The patients were asked to recall their acute symptoms during their first study visit. Many reported headaches, weakness, altered mental status, and cranial nerve symptoms. About 2% described convulsions or strokelike symptoms, and about 25% described symptoms consistent with meningitis.
It’s unclear how the virus affected the CNS, which isn’t considered to be a target organ. Perhaps fluid loss from severe diarrhea led to cerebral hypoperfusion. The cytokine storm during the acute phase might also have played a role. The virus has, however, been isolated from cerebral spinal fluid and, although uncommon, there are the reports of meningitis symptoms, so perhaps it does have direct CNS effects. Much remains to be learned.
Both cases and controls were a mean of about 35 years old, and evenly split between the sexes; 108 patients (70.6%) spent more than 2 weeks in an Ebola treatment unit.
The work was funded by the National Institutes of Health. Dr. Billioux had no disclosures.
AT ANA 2017
Key clinical point:
Major finding: A year after their acute infection, almost two-thirds of Ebola survivors had abnormal neurologic exams.
Data source: Natural history study involving 153 patients
Disclosures: The work was funded by the National Institutes of Health. The lead investigator had no disclosures.
Higher stroke risk found for TAVR versus SAVR
SAN DIEGO – There was an 86% greater risk of ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, and a more than sixfold increased risk of hemorrhagic stroke, in a review of more than 44,000 patients in the Nationwide Readmissions Database who were followed out to a year after having one procedure or the other.
“Our data suggest an elevated risk of both ischemic and hemorrhagic stroke after TAVR [transcatheter aortic valve replacement]. I see a lot of people that have strokes after” TAVR, so “I wasn’t all that surprised that there is an increased risk, but could I have guessed it would have been so high? No.” Perhaps “we are offering it to people we shouldn’t be offering it to,” said lead investigator Laura Stein, MD, a vascular neurology fellow at Mount Sinai Hospital, New York.
The 2013 Nationwide Readmissions Database used in the study captured more than 14 million readmissions in the United States across all payers and the uninsured. “We used this database because its captures all comers” and reflects “more real-world practice,” Dr. Stein said.
There were 6,015 TAVR and 38,624 SAVR cases in 2013, and the team found consistently elevated cumulative risks of ischemic and hemorrhagic stroke after TAVR, compared with SAVR, according to a presentation at the annual meeting of the American Neurological Association.
Compared with SAVR, the hazard ratio for ischemic stroke with TAVR was 1.86 (95% confidence interval, 1.12-3.08; P = .016) and, for hemorrhagic stroke, 6.17 (95% CI, 1.97-19.33; P = .0018). Dr. Stein declined to release absolute numbers of strokes in the two groups, pending publication.
“A lot of attention is being paid to this topic because there has been a push, a lot of it by the device makers, to prove that [TAVR] outcomes are just as good as with traditional surgery, and that we should be offering [TAVR] to more people with higher risk factor profiles who might not have been offered repair otherwise. Our job is to help patients make the most informed decisions. Having another source of data like [ours]” adds to the conversation about risks and benefits, she said.
The investigators adjusted for a large number of potential confounders to make sure the comparison was as fair as possible given the limits of database reviews. Among other variables, they controlled for baseline cardiovascular risk factors, carotid artery disease, heart failure, obesity, smoking, surgical complications, mortality, and illness severity scores, as well as hospital size, teaching hospital status, and urban versus rural location.
“What we can’t know is what medications these patients were on that might have increased their bleeding or ischemia risk. Also, we were relying on coding done by other people,” Dr. Stein said.
The next step is to look at the impact of stenting and other concomitant procedures. “We were surprised by the number of people that had multiple procedures at the same time.” The ultimate goal is to develop a risk score to help patients and doctors decide between the two procedures, she said.
Meanwhile, the team found no difference in stroke risk between coronary artery bypass grafting and percutaneous coronary interventions in the 2013 database.
Three was no industry funding for the work, and Dr. Stein did not have any relevant disclosures.
SAN DIEGO – There was an 86% greater risk of ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, and a more than sixfold increased risk of hemorrhagic stroke, in a review of more than 44,000 patients in the Nationwide Readmissions Database who were followed out to a year after having one procedure or the other.
“Our data suggest an elevated risk of both ischemic and hemorrhagic stroke after TAVR [transcatheter aortic valve replacement]. I see a lot of people that have strokes after” TAVR, so “I wasn’t all that surprised that there is an increased risk, but could I have guessed it would have been so high? No.” Perhaps “we are offering it to people we shouldn’t be offering it to,” said lead investigator Laura Stein, MD, a vascular neurology fellow at Mount Sinai Hospital, New York.
The 2013 Nationwide Readmissions Database used in the study captured more than 14 million readmissions in the United States across all payers and the uninsured. “We used this database because its captures all comers” and reflects “more real-world practice,” Dr. Stein said.
There were 6,015 TAVR and 38,624 SAVR cases in 2013, and the team found consistently elevated cumulative risks of ischemic and hemorrhagic stroke after TAVR, compared with SAVR, according to a presentation at the annual meeting of the American Neurological Association.
Compared with SAVR, the hazard ratio for ischemic stroke with TAVR was 1.86 (95% confidence interval, 1.12-3.08; P = .016) and, for hemorrhagic stroke, 6.17 (95% CI, 1.97-19.33; P = .0018). Dr. Stein declined to release absolute numbers of strokes in the two groups, pending publication.
“A lot of attention is being paid to this topic because there has been a push, a lot of it by the device makers, to prove that [TAVR] outcomes are just as good as with traditional surgery, and that we should be offering [TAVR] to more people with higher risk factor profiles who might not have been offered repair otherwise. Our job is to help patients make the most informed decisions. Having another source of data like [ours]” adds to the conversation about risks and benefits, she said.
The investigators adjusted for a large number of potential confounders to make sure the comparison was as fair as possible given the limits of database reviews. Among other variables, they controlled for baseline cardiovascular risk factors, carotid artery disease, heart failure, obesity, smoking, surgical complications, mortality, and illness severity scores, as well as hospital size, teaching hospital status, and urban versus rural location.
“What we can’t know is what medications these patients were on that might have increased their bleeding or ischemia risk. Also, we were relying on coding done by other people,” Dr. Stein said.
The next step is to look at the impact of stenting and other concomitant procedures. “We were surprised by the number of people that had multiple procedures at the same time.” The ultimate goal is to develop a risk score to help patients and doctors decide between the two procedures, she said.
Meanwhile, the team found no difference in stroke risk between coronary artery bypass grafting and percutaneous coronary interventions in the 2013 database.
Three was no industry funding for the work, and Dr. Stein did not have any relevant disclosures.
SAN DIEGO – There was an 86% greater risk of ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, and a more than sixfold increased risk of hemorrhagic stroke, in a review of more than 44,000 patients in the Nationwide Readmissions Database who were followed out to a year after having one procedure or the other.
“Our data suggest an elevated risk of both ischemic and hemorrhagic stroke after TAVR [transcatheter aortic valve replacement]. I see a lot of people that have strokes after” TAVR, so “I wasn’t all that surprised that there is an increased risk, but could I have guessed it would have been so high? No.” Perhaps “we are offering it to people we shouldn’t be offering it to,” said lead investigator Laura Stein, MD, a vascular neurology fellow at Mount Sinai Hospital, New York.
The 2013 Nationwide Readmissions Database used in the study captured more than 14 million readmissions in the United States across all payers and the uninsured. “We used this database because its captures all comers” and reflects “more real-world practice,” Dr. Stein said.
There were 6,015 TAVR and 38,624 SAVR cases in 2013, and the team found consistently elevated cumulative risks of ischemic and hemorrhagic stroke after TAVR, compared with SAVR, according to a presentation at the annual meeting of the American Neurological Association.
Compared with SAVR, the hazard ratio for ischemic stroke with TAVR was 1.86 (95% confidence interval, 1.12-3.08; P = .016) and, for hemorrhagic stroke, 6.17 (95% CI, 1.97-19.33; P = .0018). Dr. Stein declined to release absolute numbers of strokes in the two groups, pending publication.
“A lot of attention is being paid to this topic because there has been a push, a lot of it by the device makers, to prove that [TAVR] outcomes are just as good as with traditional surgery, and that we should be offering [TAVR] to more people with higher risk factor profiles who might not have been offered repair otherwise. Our job is to help patients make the most informed decisions. Having another source of data like [ours]” adds to the conversation about risks and benefits, she said.
The investigators adjusted for a large number of potential confounders to make sure the comparison was as fair as possible given the limits of database reviews. Among other variables, they controlled for baseline cardiovascular risk factors, carotid artery disease, heart failure, obesity, smoking, surgical complications, mortality, and illness severity scores, as well as hospital size, teaching hospital status, and urban versus rural location.
“What we can’t know is what medications these patients were on that might have increased their bleeding or ischemia risk. Also, we were relying on coding done by other people,” Dr. Stein said.
The next step is to look at the impact of stenting and other concomitant procedures. “We were surprised by the number of people that had multiple procedures at the same time.” The ultimate goal is to develop a risk score to help patients and doctors decide between the two procedures, she said.
Meanwhile, the team found no difference in stroke risk between coronary artery bypass grafting and percutaneous coronary interventions in the 2013 database.
Three was no industry funding for the work, and Dr. Stein did not have any relevant disclosures.
AT ANA 2017
Key clinical point:
Major finding: There was an 86% greater risk of ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, and a more than sixfold increased risk of hemorrhagic stroke.
Data source: Database review of more than 44,000 patients
Disclosures: Three was no industry funding for the work, and the lead investigator did not have any relevant disclosures.
CHMP recommends new formulation of pegaspargase
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for lyophilized pegaspargase (ONCASPAR).
If approved, the product would be used as a component of antineoplastic therapy in patients of all ages who have acute lymphoblastic leukemia (ALL).
The product is a freeze-dried formulation of liquid pegaspargase, which is already approved for the aforementioned indication.
The CHMP’s recommendation regarding lyophilized pegaspargase will be submitted to the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
The CHMP’s recommendation regarding lyophilized pegaspargase is based on analytical and nonclinical studies, which indicate that lyophilized pegaspargase is comparable to the liquid formulation.
Once reconstituted, lyophilized pegaspargase demonstrates similar pharmacokinetics and pharmacodynamics as liquid pegaspargase.
“Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, and, with no change in dosing regimen, it offers a 3-times longer shelf life,” said Howard B. Mayer, MD, of Shire, the company that developed lyophilized pegaspargase.
“Prolonging shelf life to 24 months for this critically important therapy facilitates management of product inventory by enabling greater flexibility and longer-term planning. Once approved, with the extended shelf life of lyophilized ONCASPAR, we also hope to improve access to the medicine for ALL patients in countries currently not offering liquid ONCASPAR.”
Lyophilized pegaspargase works in the same way as the liquid formulation. It rapidly depletes serum L-asparagine levels and interferes with protein synthesis, thereby depriving lymphoblasts of asparaginase and resulting in cell death. 
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for lyophilized pegaspargase (ONCASPAR).
If approved, the product would be used as a component of antineoplastic therapy in patients of all ages who have acute lymphoblastic leukemia (ALL).
The product is a freeze-dried formulation of liquid pegaspargase, which is already approved for the aforementioned indication.
The CHMP’s recommendation regarding lyophilized pegaspargase will be submitted to the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
The CHMP’s recommendation regarding lyophilized pegaspargase is based on analytical and nonclinical studies, which indicate that lyophilized pegaspargase is comparable to the liquid formulation.
Once reconstituted, lyophilized pegaspargase demonstrates similar pharmacokinetics and pharmacodynamics as liquid pegaspargase.
“Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, and, with no change in dosing regimen, it offers a 3-times longer shelf life,” said Howard B. Mayer, MD, of Shire, the company that developed lyophilized pegaspargase.
“Prolonging shelf life to 24 months for this critically important therapy facilitates management of product inventory by enabling greater flexibility and longer-term planning. Once approved, with the extended shelf life of lyophilized ONCASPAR, we also hope to improve access to the medicine for ALL patients in countries currently not offering liquid ONCASPAR.”
Lyophilized pegaspargase works in the same way as the liquid formulation. It rapidly depletes serum L-asparagine levels and interferes with protein synthesis, thereby depriving lymphoblasts of asparaginase and resulting in cell death.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorization for lyophilized pegaspargase (ONCASPAR).
If approved, the product would be used as a component of antineoplastic therapy in patients of all ages who have acute lymphoblastic leukemia (ALL).
The product is a freeze-dried formulation of liquid pegaspargase, which is already approved for the aforementioned indication.
The CHMP’s recommendation regarding lyophilized pegaspargase will be submitted to the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
The CHMP’s recommendation regarding lyophilized pegaspargase is based on analytical and nonclinical studies, which indicate that lyophilized pegaspargase is comparable to the liquid formulation.
Once reconstituted, lyophilized pegaspargase demonstrates similar pharmacokinetics and pharmacodynamics as liquid pegaspargase.
“Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, and, with no change in dosing regimen, it offers a 3-times longer shelf life,” said Howard B. Mayer, MD, of Shire, the company that developed lyophilized pegaspargase.
“Prolonging shelf life to 24 months for this critically important therapy facilitates management of product inventory by enabling greater flexibility and longer-term planning. Once approved, with the extended shelf life of lyophilized ONCASPAR, we also hope to improve access to the medicine for ALL patients in countries currently not offering liquid ONCASPAR.”
Lyophilized pegaspargase works in the same way as the liquid formulation. It rapidly depletes serum L-asparagine levels and interferes with protein synthesis, thereby depriving lymphoblasts of asparaginase and resulting in cell death.
Ciprofloxacin cured gyrA wild-type Neisseria gonorrhoeae infections
SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.
“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.
The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.
Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.
Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.
Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.
“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.
The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.
Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.
Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.
Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.
“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.
The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.
Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.
Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.
Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
AT IDWEEK 2017
Key clinical point:
Major finding: The cure rate was 100% among 25 patients who received ciprofloxacin for wild-type gyrA gonorrhea.
Data source: A single-center study of 582 patients with gonorrhea.
Disclosures: The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
Rectal swabs concurred with stool tests in children with GI illness
SAN DIEGO – Clinicians who treat children with acute gastrointestinal illness should consider testing rectal swabs when they need to rapidly identify enteropathogens and cannot immediately obtain a bulk stool sample, Stephen Freedman, MD, said at an annual scientific meeting on infectious diseases.
Among 1,519 children and adolescents with diarrhea, vomiting, or both symptoms, diagnostic yields of paired stool and rectal swab specimens were 76% and 68%, respectively, Dr. Freedman reported on behalf of the Alberta Provincial Pediatric Enteric Infection Team.
Kappa values for concordance were 0.76 overall (95% confidence interval [CI], 0.71-0.80), .82 for viruses (0.79-0.86), and .74 for bacteria (0.68-0.80). A kappa value between 0.61 and 0.80 indicates “substantial” concordance between two results, while a value between 0.81 and 1.0 suggests “near perfect” concordance, explained Dr. Freedman of the University of Calgary (Alta.). In addition, 95% of health care providers and 82% of home caregivers considered rectal swabs easy to use, while 10% considered them unacceptable. “Recommendations against rectal swab use should be reconsidered,” he said.
Traditional testing of diarrheal bulk stool is highly specific, but burdensome and subject to various handling issues that can substantially delay diagnosis and outbreak detection, Dr. Freedman said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“Flocked rectal swabs are used at the point of care and are quick and acceptable, but there are few precedents in the literature for their use in children or in patients with vomiting without diarrhea,” he said.
To help fill that gap, the researchers collected 1,147 stool specimens and 1,468 rectal swabs from patients under age 18 years who were seen at emergency departments in Calgary and Edmonton for diarrhea, vomiting, or both, with at least three episodes in the previous 24 hours. All of the patients had been ill for less than 7 days and had no detected psychiatric illness or neutropenia. Stool and rectal samples were evaluated three ways – by routine enteric bacterial culture, an in-house gastroenteric viral panel, and with the polymerase chain reaction-based Luminex xTAG Gastrointestinal Pathogen Panel. Swabs were taken by rotating them 360 degrees one time within the anus. Stool and swab specimens collected at home were stored at room temperature for less than 12 hours.
Among all paired specimens, 76% of stool samples and 68% of rectal swabs tested positive for at least one pathogen (P less than .0001). Thus, stool testing had about a 30% higher odds of detection than did swab testing in the same patient (OR, 1.3; 95% CI, 1.3-1.5). Odds ratios also favored stool testing in subgroups of patients with diarrhea (OR, 1.2; 95% CI, 1.1-1.4) or isolated vomiting (OR, 1.8; 95% CI, 1.5-2.1).
However, many stool specimens were never submitted, Dr. Freedman said. When the researchers assumed that these unsubmitted samples all tested negative, the diagnostic yield of stool samples fell to 57% and several odds ratios inverted in favor of rectal swabs. The study findings did not change when the researchers excluded positive results for Clostridium difficile in children younger than 2 years or when they restricted the analysis to paired specimens obtained within 24 hours.
The researchers are continuing to explore the diagnostic yield of rectal swab tests for multidrug-resistant pathogens, including those that are notifiable to public health departments, Dr. Freedman said.
Dr. Freedman disclosed ties to Copan Diagnostics, Luminex, and Alere.
SAN DIEGO – Clinicians who treat children with acute gastrointestinal illness should consider testing rectal swabs when they need to rapidly identify enteropathogens and cannot immediately obtain a bulk stool sample, Stephen Freedman, MD, said at an annual scientific meeting on infectious diseases.
Among 1,519 children and adolescents with diarrhea, vomiting, or both symptoms, diagnostic yields of paired stool and rectal swab specimens were 76% and 68%, respectively, Dr. Freedman reported on behalf of the Alberta Provincial Pediatric Enteric Infection Team.
Kappa values for concordance were 0.76 overall (95% confidence interval [CI], 0.71-0.80), .82 for viruses (0.79-0.86), and .74 for bacteria (0.68-0.80). A kappa value between 0.61 and 0.80 indicates “substantial” concordance between two results, while a value between 0.81 and 1.0 suggests “near perfect” concordance, explained Dr. Freedman of the University of Calgary (Alta.). In addition, 95% of health care providers and 82% of home caregivers considered rectal swabs easy to use, while 10% considered them unacceptable. “Recommendations against rectal swab use should be reconsidered,” he said.
Traditional testing of diarrheal bulk stool is highly specific, but burdensome and subject to various handling issues that can substantially delay diagnosis and outbreak detection, Dr. Freedman said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“Flocked rectal swabs are used at the point of care and are quick and acceptable, but there are few precedents in the literature for their use in children or in patients with vomiting without diarrhea,” he said.
To help fill that gap, the researchers collected 1,147 stool specimens and 1,468 rectal swabs from patients under age 18 years who were seen at emergency departments in Calgary and Edmonton for diarrhea, vomiting, or both, with at least three episodes in the previous 24 hours. All of the patients had been ill for less than 7 days and had no detected psychiatric illness or neutropenia. Stool and rectal samples were evaluated three ways – by routine enteric bacterial culture, an in-house gastroenteric viral panel, and with the polymerase chain reaction-based Luminex xTAG Gastrointestinal Pathogen Panel. Swabs were taken by rotating them 360 degrees one time within the anus. Stool and swab specimens collected at home were stored at room temperature for less than 12 hours.
Among all paired specimens, 76% of stool samples and 68% of rectal swabs tested positive for at least one pathogen (P less than .0001). Thus, stool testing had about a 30% higher odds of detection than did swab testing in the same patient (OR, 1.3; 95% CI, 1.3-1.5). Odds ratios also favored stool testing in subgroups of patients with diarrhea (OR, 1.2; 95% CI, 1.1-1.4) or isolated vomiting (OR, 1.8; 95% CI, 1.5-2.1).
However, many stool specimens were never submitted, Dr. Freedman said. When the researchers assumed that these unsubmitted samples all tested negative, the diagnostic yield of stool samples fell to 57% and several odds ratios inverted in favor of rectal swabs. The study findings did not change when the researchers excluded positive results for Clostridium difficile in children younger than 2 years or when they restricted the analysis to paired specimens obtained within 24 hours.
The researchers are continuing to explore the diagnostic yield of rectal swab tests for multidrug-resistant pathogens, including those that are notifiable to public health departments, Dr. Freedman said.
Dr. Freedman disclosed ties to Copan Diagnostics, Luminex, and Alere.
SAN DIEGO – Clinicians who treat children with acute gastrointestinal illness should consider testing rectal swabs when they need to rapidly identify enteropathogens and cannot immediately obtain a bulk stool sample, Stephen Freedman, MD, said at an annual scientific meeting on infectious diseases.
Among 1,519 children and adolescents with diarrhea, vomiting, or both symptoms, diagnostic yields of paired stool and rectal swab specimens were 76% and 68%, respectively, Dr. Freedman reported on behalf of the Alberta Provincial Pediatric Enteric Infection Team.
Kappa values for concordance were 0.76 overall (95% confidence interval [CI], 0.71-0.80), .82 for viruses (0.79-0.86), and .74 for bacteria (0.68-0.80). A kappa value between 0.61 and 0.80 indicates “substantial” concordance between two results, while a value between 0.81 and 1.0 suggests “near perfect” concordance, explained Dr. Freedman of the University of Calgary (Alta.). In addition, 95% of health care providers and 82% of home caregivers considered rectal swabs easy to use, while 10% considered them unacceptable. “Recommendations against rectal swab use should be reconsidered,” he said.
Traditional testing of diarrheal bulk stool is highly specific, but burdensome and subject to various handling issues that can substantially delay diagnosis and outbreak detection, Dr. Freedman said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“Flocked rectal swabs are used at the point of care and are quick and acceptable, but there are few precedents in the literature for their use in children or in patients with vomiting without diarrhea,” he said.
To help fill that gap, the researchers collected 1,147 stool specimens and 1,468 rectal swabs from patients under age 18 years who were seen at emergency departments in Calgary and Edmonton for diarrhea, vomiting, or both, with at least three episodes in the previous 24 hours. All of the patients had been ill for less than 7 days and had no detected psychiatric illness or neutropenia. Stool and rectal samples were evaluated three ways – by routine enteric bacterial culture, an in-house gastroenteric viral panel, and with the polymerase chain reaction-based Luminex xTAG Gastrointestinal Pathogen Panel. Swabs were taken by rotating them 360 degrees one time within the anus. Stool and swab specimens collected at home were stored at room temperature for less than 12 hours.
Among all paired specimens, 76% of stool samples and 68% of rectal swabs tested positive for at least one pathogen (P less than .0001). Thus, stool testing had about a 30% higher odds of detection than did swab testing in the same patient (OR, 1.3; 95% CI, 1.3-1.5). Odds ratios also favored stool testing in subgroups of patients with diarrhea (OR, 1.2; 95% CI, 1.1-1.4) or isolated vomiting (OR, 1.8; 95% CI, 1.5-2.1).
However, many stool specimens were never submitted, Dr. Freedman said. When the researchers assumed that these unsubmitted samples all tested negative, the diagnostic yield of stool samples fell to 57% and several odds ratios inverted in favor of rectal swabs. The study findings did not change when the researchers excluded positive results for Clostridium difficile in children younger than 2 years or when they restricted the analysis to paired specimens obtained within 24 hours.
The researchers are continuing to explore the diagnostic yield of rectal swab tests for multidrug-resistant pathogens, including those that are notifiable to public health departments, Dr. Freedman said.
Dr. Freedman disclosed ties to Copan Diagnostics, Luminex, and Alere.
AT IDWEEK 2017
Key clinical point: and cannot immediately obtain a bulk stool sample.
Major finding: Diagnostic yields of paired stool and rectal swab specimens were 76% and 68%, respectively.
Data source: A multicenter retrospective cohort study of 1,519 children and adolescents with acute-onset diarrhea, vomiting, or both.
Disclosures: Dr. Freedman disclosed ties to Copan Diagnostics, Luminex, and Alere.