Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

aotto@mdedge.com

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

aotto@mdedge.com

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

aotto@mdedge.com

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

aotto@mdedge.com

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

aotto@mdedge.com

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

aotto@mdedge.com

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

ORLANDO – Intraperitoneal infusions of peginterferon alfa-2b and interferon gamma-1b, administered with or without autologous monocytes, showed antitumor activity and tolerability in heavily pretreated patients with ovarian cancer in a first-in-human study.

Sharon Worcester/MDedge News

The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.

Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.

The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).

In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
 

Results

Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.

One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).

The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.

Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.

There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
 

Rationale and next steps

“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”

“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.

The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.

The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.

The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.

In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.

He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.

“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”

The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.

sworcester@mdedge.com

SOURCE: Cole C et al. ASCO-SITC: Abstract 1.

ORLANDO – Intraperitoneal infusions of peginterferon alfa-2b and interferon gamma-1b, administered with or without autologous monocytes, showed antitumor activity and tolerability in heavily pretreated patients with ovarian cancer in a first-in-human study.

Sharon Worcester/MDedge News

The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.

Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.

The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).

In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
 

Results

Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.

One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).

The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.

Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.

There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
 

Rationale and next steps

“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”

“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.

The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.

The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.

The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.

In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.

He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.

“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”

The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.

sworcester@mdedge.com

SOURCE: Cole C et al. ASCO-SITC: Abstract 1.

ORLANDO – Intraperitoneal infusions of peginterferon alfa-2b and interferon gamma-1b, administered with or without autologous monocytes, showed antitumor activity and tolerability in heavily pretreated patients with ovarian cancer in a first-in-human study.

Sharon Worcester/MDedge News

The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.

Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.

The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).

In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
 

Results

Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.

One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).

The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.

Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.

There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
 

Rationale and next steps

“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”

“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.

The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.

The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.

The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.

In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.

He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.

“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”

The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.

sworcester@mdedge.com

SOURCE: Cole C et al. ASCO-SITC: Abstract 1.