Recent findings support the use of multimodal magnetic resonance (MR) imaging to distinguish migraine with aura from stroke and the simultaneous use of these MR imaging sequences to improve understanding of perfusion changes during migraine with aura. Hemiplegic migraine is a common cause of acute brain attack in pediatrics. MR imaging sequences useful in differentiating hemiplegic migraine from other entities include arterial spin-labeling, susceptibility-weighted imaging (SWI), magnetic resonance angiography (MRA), and diffusion-weighted imaging (DWI). Researchers evaluated 12 pediatric patients with acute hemiplegic migraine or migraine with aura who underwent MR imaging within 12 hours of symptom onset. Quantitative and qualitative analyses were performed on arterial spin-labeling, and qualitative analysis, on SWI and MRA sequences. They found:

• All 12 patients had normal DWI and abnormal arterial spin-labeling findings.
• Furthermore, a more rapid transition from hypoperfusion to rebound hyperperfusion was observed in 3 patients compared with prior reports.

Cobb-Pitstick KM, Munjal N, Safier R, Cummings DD, Zuccoli G. Time course of cerebral perfusion changes in children with migraine with aura mimicking stroke. Am J Neuroradiol.

2018;39(9):1751-1755. doi:10.3174/ajnr.A5693.

Recent findings support the use of multimodal magnetic resonance (MR) imaging to distinguish migraine with aura from stroke and the simultaneous use of these MR imaging sequences to improve understanding of perfusion changes during migraine with aura. Hemiplegic migraine is a common cause of acute brain attack in pediatrics. MR imaging sequences useful in differentiating hemiplegic migraine from other entities include arterial spin-labeling, susceptibility-weighted imaging (SWI), magnetic resonance angiography (MRA), and diffusion-weighted imaging (DWI). Researchers evaluated 12 pediatric patients with acute hemiplegic migraine or migraine with aura who underwent MR imaging within 12 hours of symptom onset. Quantitative and qualitative analyses were performed on arterial spin-labeling, and qualitative analysis, on SWI and MRA sequences. They found:

• All 12 patients had normal DWI and abnormal arterial spin-labeling findings.
• Furthermore, a more rapid transition from hypoperfusion to rebound hyperperfusion was observed in 3 patients compared with prior reports.

Cobb-Pitstick KM, Munjal N, Safier R, Cummings DD, Zuccoli G. Time course of cerebral perfusion changes in children with migraine with aura mimicking stroke. Am J Neuroradiol.

2018;39(9):1751-1755. doi:10.3174/ajnr.A5693.

Recent findings support the use of multimodal magnetic resonance (MR) imaging to distinguish migraine with aura from stroke and the simultaneous use of these MR imaging sequences to improve understanding of perfusion changes during migraine with aura. Hemiplegic migraine is a common cause of acute brain attack in pediatrics. MR imaging sequences useful in differentiating hemiplegic migraine from other entities include arterial spin-labeling, susceptibility-weighted imaging (SWI), magnetic resonance angiography (MRA), and diffusion-weighted imaging (DWI). Researchers evaluated 12 pediatric patients with acute hemiplegic migraine or migraine with aura who underwent MR imaging within 12 hours of symptom onset. Quantitative and qualitative analyses were performed on arterial spin-labeling, and qualitative analysis, on SWI and MRA sequences. They found:

• All 12 patients had normal DWI and abnormal arterial spin-labeling findings.
• Furthermore, a more rapid transition from hypoperfusion to rebound hyperperfusion was observed in 3 patients compared with prior reports.

Cobb-Pitstick KM, Munjal N, Safier R, Cummings DD, Zuccoli G. Time course of cerebral perfusion changes in children with migraine with aura mimicking stroke. Am J Neuroradiol.

2018;39(9):1751-1755. doi:10.3174/ajnr.A5693.

Emergency department (ED) visits for migraine are burdensome to patients and to the larger healthcare system and society, a recent study found. Furthermore, a substantial number of headache specialists are dissatisfied with the care their patients receive in the ED. Researchers

surveyed members of the American Headache Society (AHS) Emergency Department/Refractory/Inpatient (EDRI) Section to understand their practice regarding patients who call their office to be seen urgently, and to understand their communication with local EDs. There were 96 eligible AHS members, 50 of whom responded to questionnaires either by email or in person (52%).They found:

• Of total respondents, 59% reported giving rescue treatment to their patients to manage acute attacks.
• 54% reported using standard protocols for outpatients not responding to usual acute treatments.
• In the event of a request for urgent care, 12% of specialists reported bringing patients into the office most or all of the time, and 20% reported sending patients to the ED some or most of the time for headache management.
• 60% reported that their ED has a protocol for migraine management.

Minen MT, Ortega E, Lipton RB, Cowan R. American Headache Society survey about urgent and emergency management of headache patients. [Published online ahead of print September 12, 2018]. Headache. doi:10.1111/head.13387.

Emergency department (ED) visits for migraine are burdensome to patients and to the larger healthcare system and society, a recent study found. Furthermore, a substantial number of headache specialists are dissatisfied with the care their patients receive in the ED. Researchers

surveyed members of the American Headache Society (AHS) Emergency Department/Refractory/Inpatient (EDRI) Section to understand their practice regarding patients who call their office to be seen urgently, and to understand their communication with local EDs. There were 96 eligible AHS members, 50 of whom responded to questionnaires either by email or in person (52%).They found:

• Of total respondents, 59% reported giving rescue treatment to their patients to manage acute attacks.
• 54% reported using standard protocols for outpatients not responding to usual acute treatments.
• In the event of a request for urgent care, 12% of specialists reported bringing patients into the office most or all of the time, and 20% reported sending patients to the ED some or most of the time for headache management.
• 60% reported that their ED has a protocol for migraine management.

Minen MT, Ortega E, Lipton RB, Cowan R. American Headache Society survey about urgent and emergency management of headache patients. [Published online ahead of print September 12, 2018]. Headache. doi:10.1111/head.13387.

Emergency department (ED) visits for migraine are burdensome to patients and to the larger healthcare system and society, a recent study found. Furthermore, a substantial number of headache specialists are dissatisfied with the care their patients receive in the ED. Researchers

surveyed members of the American Headache Society (AHS) Emergency Department/Refractory/Inpatient (EDRI) Section to understand their practice regarding patients who call their office to be seen urgently, and to understand their communication with local EDs. There were 96 eligible AHS members, 50 of whom responded to questionnaires either by email or in person (52%).They found:

• Of total respondents, 59% reported giving rescue treatment to their patients to manage acute attacks.
• 54% reported using standard protocols for outpatients not responding to usual acute treatments.
• In the event of a request for urgent care, 12% of specialists reported bringing patients into the office most or all of the time, and 20% reported sending patients to the ED some or most of the time for headache management.
• 60% reported that their ED has a protocol for migraine management.

Minen MT, Ortega E, Lipton RB, Cowan R. American Headache Society survey about urgent and emergency management of headache patients. [Published online ahead of print September 12, 2018]. Headache. doi:10.1111/head.13387.

New York – For unfit elderly patients with acute myeloid leukemia (AML), venetoclax may be one of the most promising potential options that is emerging, according to an expert in the field.

National Institutes of Health/Wikimedia Commons/Public Domain

The oral B-cell lymphoma 2 (BCL-2) inhibitor is the treatment that some in the AML community are “most excited about” for this population, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said at the National Comprehensive Cancer Network (NCCN) Annual Congress: Hematologic Malignancies.

Venetoclax is currently approved by the Food and Drug Administration for previously treated chronic lymphocytic leukemia (CLL), alone or in combination with rituximab. It has been granted four Breakthrough Therapy designations from the FDA in AML. In July 2018, AbbVie submitted a Supplemental New Drug Application to the FDA for its use in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed AML patients who are ineligible for intensive chemotherapy.

“This agent doesn’t work on its own but had worked in the refractory setting and can be a great option upfront,” Dr. Wang said.

About half the patients were alive at 1 year following treatment with venetoclax plus low-dose chemotherapy, whether that was LDAC or an HMA, she said, commenting on recently reported results.

In a phase 1b trial, venetoclax was evaluated in combination with either azacitidine or decitabine. In recently reported preliminary results that included 57 patients aged 65 years or older who were ineligible for standard induction therapy, the combination was well tolerated and had promising activity (Lancet Oncol. 2018 Feb;19[2]:216-28).

Overall, 35 patients (61%) had complete remission (CR) or complete remission with incomplete marrow recovery (CRi).

In another report on this same trial, which included 33 patients from a single participating center who received venetoclax and azacytidine, the overall response rate was 91%, including 19 (58%) with CR and 9 (27%) with CRi (Blood. 2017 Dec;130 [Suppl 1]:181).

A separate phase 1/2 trial examined venetoclax plus LDAC in treatment-naive elderly patients unfit for intensive chemotherapy. In the 1-year outcomes that have been reported, the observed CR/CRi rate was 62%, median overall survival was an “encouraging” 11.4 months, and the observed 12-month overall survival was 46% in 61 patients treated at a venetoclax dose of 600 mg (Blood. 2017 Dec;130 [Suppl 1]:890).

In those 61 patients, treatment-related grade 3/4 adverse events included thrombocytopenia in 59%, neutropenia in 46%, febrile neutropenia in 36%, anemia in 28%, decreased white blood cell count in 26%, and one case of tumor lysis syndrome, according to the report.

Based on those findings in a cohort of patients with poor risk features, venetoclax 600 mg plus LDAC was carried forward to be evaluated in an ongoing phase 3 study, investigators noted at the time.

Dr. Wang reported financial relationships with AbbVie, Amgen, ImmunoGen, Incyte, Novartis, and Otsuka.

New York – For unfit elderly patients with acute myeloid leukemia (AML), venetoclax may be one of the most promising potential options that is emerging, according to an expert in the field.

National Institutes of Health/Wikimedia Commons/Public Domain

The oral B-cell lymphoma 2 (BCL-2) inhibitor is the treatment that some in the AML community are “most excited about” for this population, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said at the National Comprehensive Cancer Network (NCCN) Annual Congress: Hematologic Malignancies.

Venetoclax is currently approved by the Food and Drug Administration for previously treated chronic lymphocytic leukemia (CLL), alone or in combination with rituximab. It has been granted four Breakthrough Therapy designations from the FDA in AML. In July 2018, AbbVie submitted a Supplemental New Drug Application to the FDA for its use in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed AML patients who are ineligible for intensive chemotherapy.

“This agent doesn’t work on its own but had worked in the refractory setting and can be a great option upfront,” Dr. Wang said.

About half the patients were alive at 1 year following treatment with venetoclax plus low-dose chemotherapy, whether that was LDAC or an HMA, she said, commenting on recently reported results.

In a phase 1b trial, venetoclax was evaluated in combination with either azacitidine or decitabine. In recently reported preliminary results that included 57 patients aged 65 years or older who were ineligible for standard induction therapy, the combination was well tolerated and had promising activity (Lancet Oncol. 2018 Feb;19[2]:216-28).

Overall, 35 patients (61%) had complete remission (CR) or complete remission with incomplete marrow recovery (CRi).

In another report on this same trial, which included 33 patients from a single participating center who received venetoclax and azacytidine, the overall response rate was 91%, including 19 (58%) with CR and 9 (27%) with CRi (Blood. 2017 Dec;130 [Suppl 1]:181).

A separate phase 1/2 trial examined venetoclax plus LDAC in treatment-naive elderly patients unfit for intensive chemotherapy. In the 1-year outcomes that have been reported, the observed CR/CRi rate was 62%, median overall survival was an “encouraging” 11.4 months, and the observed 12-month overall survival was 46% in 61 patients treated at a venetoclax dose of 600 mg (Blood. 2017 Dec;130 [Suppl 1]:890).

In those 61 patients, treatment-related grade 3/4 adverse events included thrombocytopenia in 59%, neutropenia in 46%, febrile neutropenia in 36%, anemia in 28%, decreased white blood cell count in 26%, and one case of tumor lysis syndrome, according to the report.

Based on those findings in a cohort of patients with poor risk features, venetoclax 600 mg plus LDAC was carried forward to be evaluated in an ongoing phase 3 study, investigators noted at the time.

Dr. Wang reported financial relationships with AbbVie, Amgen, ImmunoGen, Incyte, Novartis, and Otsuka.

New York – For unfit elderly patients with acute myeloid leukemia (AML), venetoclax may be one of the most promising potential options that is emerging, according to an expert in the field.

National Institutes of Health/Wikimedia Commons/Public Domain

The oral B-cell lymphoma 2 (BCL-2) inhibitor is the treatment that some in the AML community are “most excited about” for this population, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said at the National Comprehensive Cancer Network (NCCN) Annual Congress: Hematologic Malignancies.

Venetoclax is currently approved by the Food and Drug Administration for previously treated chronic lymphocytic leukemia (CLL), alone or in combination with rituximab. It has been granted four Breakthrough Therapy designations from the FDA in AML. In July 2018, AbbVie submitted a Supplemental New Drug Application to the FDA for its use in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed AML patients who are ineligible for intensive chemotherapy.

“This agent doesn’t work on its own but had worked in the refractory setting and can be a great option upfront,” Dr. Wang said.

About half the patients were alive at 1 year following treatment with venetoclax plus low-dose chemotherapy, whether that was LDAC or an HMA, she said, commenting on recently reported results.

In a phase 1b trial, venetoclax was evaluated in combination with either azacitidine or decitabine. In recently reported preliminary results that included 57 patients aged 65 years or older who were ineligible for standard induction therapy, the combination was well tolerated and had promising activity (Lancet Oncol. 2018 Feb;19[2]:216-28).

Overall, 35 patients (61%) had complete remission (CR) or complete remission with incomplete marrow recovery (CRi).

In another report on this same trial, which included 33 patients from a single participating center who received venetoclax and azacytidine, the overall response rate was 91%, including 19 (58%) with CR and 9 (27%) with CRi (Blood. 2017 Dec;130 [Suppl 1]:181).

A separate phase 1/2 trial examined venetoclax plus LDAC in treatment-naive elderly patients unfit for intensive chemotherapy. In the 1-year outcomes that have been reported, the observed CR/CRi rate was 62%, median overall survival was an “encouraging” 11.4 months, and the observed 12-month overall survival was 46% in 61 patients treated at a venetoclax dose of 600 mg (Blood. 2017 Dec;130 [Suppl 1]:890).

In those 61 patients, treatment-related grade 3/4 adverse events included thrombocytopenia in 59%, neutropenia in 46%, febrile neutropenia in 36%, anemia in 28%, decreased white blood cell count in 26%, and one case of tumor lysis syndrome, according to the report.

Based on those findings in a cohort of patients with poor risk features, venetoclax 600 mg plus LDAC was carried forward to be evaluated in an ongoing phase 3 study, investigators noted at the time.

Dr. Wang reported financial relationships with AbbVie, Amgen, ImmunoGen, Incyte, Novartis, and Otsuka.

Researchers discovered 10.7% prevalence of migraines and synergism between female gender and stress on risk of migraine in a recent study, suggesting health interventions targeting women under stress may be beneficial. This analysis was based on data from 42,282 persons aged ≥12 years who participated in a 2013–2014 community health survey. A multivariate log-binomial model was used to calculate adjusted prevalence ratios for migraines associated with individual and joint exposures of female gender and stress. Researchers used relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S index) to measure additive interaction. They found:

• The adjusted prevalence ratios were 2.37 for female vs male, 1.63 for persons with high vs low levels of stress, and 3.38 for women with high stress vs men with low stress.
• The RERI estimate was 0.38, the AP estimate was 0.11, and the S index was 1.19.

Slatculescu AM, Chen Y. Synergism between female gender and high levels of daily stress associated with migraine headaches in Ontario, Canada. [Published online ahead of print August 28, 2018]. Neuroepidemiol. doi:10.1159/000492503.

Researchers discovered 10.7% prevalence of migraines and synergism between female gender and stress on risk of migraine in a recent study, suggesting health interventions targeting women under stress may be beneficial. This analysis was based on data from 42,282 persons aged ≥12 years who participated in a 2013–2014 community health survey. A multivariate log-binomial model was used to calculate adjusted prevalence ratios for migraines associated with individual and joint exposures of female gender and stress. Researchers used relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S index) to measure additive interaction. They found:

• The adjusted prevalence ratios were 2.37 for female vs male, 1.63 for persons with high vs low levels of stress, and 3.38 for women with high stress vs men with low stress.
• The RERI estimate was 0.38, the AP estimate was 0.11, and the S index was 1.19.

Slatculescu AM, Chen Y. Synergism between female gender and high levels of daily stress associated with migraine headaches in Ontario, Canada. [Published online ahead of print August 28, 2018]. Neuroepidemiol. doi:10.1159/000492503.

Researchers discovered 10.7% prevalence of migraines and synergism between female gender and stress on risk of migraine in a recent study, suggesting health interventions targeting women under stress may be beneficial. This analysis was based on data from 42,282 persons aged ≥12 years who participated in a 2013–2014 community health survey. A multivariate log-binomial model was used to calculate adjusted prevalence ratios for migraines associated with individual and joint exposures of female gender and stress. Researchers used relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S index) to measure additive interaction. They found:

• The adjusted prevalence ratios were 2.37 for female vs male, 1.63 for persons with high vs low levels of stress, and 3.38 for women with high stress vs men with low stress.
• The RERI estimate was 0.38, the AP estimate was 0.11, and the S index was 1.19.

Slatculescu AM, Chen Y. Synergism between female gender and high levels of daily stress associated with migraine headaches in Ontario, Canada. [Published online ahead of print August 28, 2018]. Neuroepidemiol. doi:10.1159/000492503.

Ilustration: Niklas Elmehed. (c) Nobel Media AB 2018

Two immunologists have been awarded the Nobel Prize in Physiology or Medicine for discoveries that represent a “paradigmatic shift in the fight against cancer,” the Nobel committee said.

James P. Allison, PhD, of MD Anderson Cancer Center, and Tasuku Honjo, MD, PhD, of Kyoto University, shared the prize for their discovery of cancer therapies that work by inhibiting negative immune regulation.

Dr. Allison studied the protein CTLA-4 found on T cells, which acts as a T-cell brake, and Dr. Honjo discovered a protein on immune cells called PD-1 that also acts as a T-cell brake.

In addition to sharing the honor, the scientists will split the 9 million Swedish kronor ($1.01 million) that comes with the prize.

Drs. Allison and Honjo, working in parallel, pursued different strategies for inhibiting the brakes on the immune system. Both strategies produced effective checkpoint inhibitors in the treatment of cancer.

James P. Allison

Dr. Allison was one of several scientists during the 1990s who noticed that CTLA-4 functions as a brake on T cells. Unlike other scientists, however, he set out to investigate whether blocking CTLA-4 with an antibody he had already developed could release the brake on the immune system.

The antibody had “spectacular” effects in curing mice with cancer. Despite little interest from the pharmaceutical industry, Dr. Allison continued efforts to develop the antibody therapy for humans.

The antibody turned out to be ipilimumab, which was approved in 2011 by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma.

Tasuko Honjo

A few years prior to Dr. Allison’s finding, Dr. Honjo discovered PD-1 and set out to determine its function. PD-1 also operates as a T-cell brake, but it uses a different mechanism than does CTLA-4.

Dr. Honjo and others demonstrated in animal experiments that PD-1 blockade could be an effective anticancer therapy. Over the years he demonstrated the efficacy of targeting PD-1 in different types of human cancers.

The first two PD-1 checkpoint inhibitors—pembrolizumab and nivolumab—were approved by the FDA in 2014 for the treatment of melanoma.

Nivolumab is also approved to treat classical Hodgkin lymphoma (HL), non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell carcinoma of the head and neck, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, urothelial carcinoma, and microsatellite instability-high or mismatch repair deficient colorectal cancer.

Pembrolizumab is also approved to treat primary mediastinal large B-cell lymphoma, advanced NSCLC, classical HL, advanced gastric cancer, advanced cervical cancer, head and neck squamous cell cancer, advanced urothelial bladder cancer, and microsatellite instability-high cancer.

And targeting both CTLA-4 and PD-1 in combination therapy together may prove to be even more effective in eliminating cancer cells than either strategy alone, as is being demonstrated in patients with melanoma.

The Nobel organization wrote in a press release, “Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed.” 

Ilustration: Niklas Elmehed. (c) Nobel Media AB 2018

Two immunologists have been awarded the Nobel Prize in Physiology or Medicine for discoveries that represent a “paradigmatic shift in the fight against cancer,” the Nobel committee said.

James P. Allison, PhD, of MD Anderson Cancer Center, and Tasuku Honjo, MD, PhD, of Kyoto University, shared the prize for their discovery of cancer therapies that work by inhibiting negative immune regulation.

Dr. Allison studied the protein CTLA-4 found on T cells, which acts as a T-cell brake, and Dr. Honjo discovered a protein on immune cells called PD-1 that also acts as a T-cell brake.

In addition to sharing the honor, the scientists will split the 9 million Swedish kronor ($1.01 million) that comes with the prize.

Drs. Allison and Honjo, working in parallel, pursued different strategies for inhibiting the brakes on the immune system. Both strategies produced effective checkpoint inhibitors in the treatment of cancer.

James P. Allison

Dr. Allison was one of several scientists during the 1990s who noticed that CTLA-4 functions as a brake on T cells. Unlike other scientists, however, he set out to investigate whether blocking CTLA-4 with an antibody he had already developed could release the brake on the immune system.

The antibody had “spectacular” effects in curing mice with cancer. Despite little interest from the pharmaceutical industry, Dr. Allison continued efforts to develop the antibody therapy for humans.

The antibody turned out to be ipilimumab, which was approved in 2011 by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma.

Tasuko Honjo

A few years prior to Dr. Allison’s finding, Dr. Honjo discovered PD-1 and set out to determine its function. PD-1 also operates as a T-cell brake, but it uses a different mechanism than does CTLA-4.

Dr. Honjo and others demonstrated in animal experiments that PD-1 blockade could be an effective anticancer therapy. Over the years he demonstrated the efficacy of targeting PD-1 in different types of human cancers.

The first two PD-1 checkpoint inhibitors—pembrolizumab and nivolumab—were approved by the FDA in 2014 for the treatment of melanoma.

Nivolumab is also approved to treat classical Hodgkin lymphoma (HL), non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell carcinoma of the head and neck, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, urothelial carcinoma, and microsatellite instability-high or mismatch repair deficient colorectal cancer.

Pembrolizumab is also approved to treat primary mediastinal large B-cell lymphoma, advanced NSCLC, classical HL, advanced gastric cancer, advanced cervical cancer, head and neck squamous cell cancer, advanced urothelial bladder cancer, and microsatellite instability-high cancer.

And targeting both CTLA-4 and PD-1 in combination therapy together may prove to be even more effective in eliminating cancer cells than either strategy alone, as is being demonstrated in patients with melanoma.

The Nobel organization wrote in a press release, “Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed.” 

Ilustration: Niklas Elmehed. (c) Nobel Media AB 2018

Two immunologists have been awarded the Nobel Prize in Physiology or Medicine for discoveries that represent a “paradigmatic shift in the fight against cancer,” the Nobel committee said.

James P. Allison, PhD, of MD Anderson Cancer Center, and Tasuku Honjo, MD, PhD, of Kyoto University, shared the prize for their discovery of cancer therapies that work by inhibiting negative immune regulation.

Dr. Allison studied the protein CTLA-4 found on T cells, which acts as a T-cell brake, and Dr. Honjo discovered a protein on immune cells called PD-1 that also acts as a T-cell brake.

In addition to sharing the honor, the scientists will split the 9 million Swedish kronor ($1.01 million) that comes with the prize.

Drs. Allison and Honjo, working in parallel, pursued different strategies for inhibiting the brakes on the immune system. Both strategies produced effective checkpoint inhibitors in the treatment of cancer.

James P. Allison

Dr. Allison was one of several scientists during the 1990s who noticed that CTLA-4 functions as a brake on T cells. Unlike other scientists, however, he set out to investigate whether blocking CTLA-4 with an antibody he had already developed could release the brake on the immune system.

The antibody had “spectacular” effects in curing mice with cancer. Despite little interest from the pharmaceutical industry, Dr. Allison continued efforts to develop the antibody therapy for humans.

The antibody turned out to be ipilimumab, which was approved in 2011 by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma.

Tasuko Honjo

A few years prior to Dr. Allison’s finding, Dr. Honjo discovered PD-1 and set out to determine its function. PD-1 also operates as a T-cell brake, but it uses a different mechanism than does CTLA-4.

Dr. Honjo and others demonstrated in animal experiments that PD-1 blockade could be an effective anticancer therapy. Over the years he demonstrated the efficacy of targeting PD-1 in different types of human cancers.

The first two PD-1 checkpoint inhibitors—pembrolizumab and nivolumab—were approved by the FDA in 2014 for the treatment of melanoma.

Nivolumab is also approved to treat classical Hodgkin lymphoma (HL), non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell carcinoma of the head and neck, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, urothelial carcinoma, and microsatellite instability-high or mismatch repair deficient colorectal cancer.

Pembrolizumab is also approved to treat primary mediastinal large B-cell lymphoma, advanced NSCLC, classical HL, advanced gastric cancer, advanced cervical cancer, head and neck squamous cell cancer, advanced urothelial bladder cancer, and microsatellite instability-high cancer.

And targeting both CTLA-4 and PD-1 in combination therapy together may prove to be even more effective in eliminating cancer cells than either strategy alone, as is being demonstrated in patients with melanoma.

The Nobel organization wrote in a press release, “Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed.” 

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

msullivan@mdedge.com

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

msullivan@mdedge.com

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

msullivan@mdedge.com

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
 

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
 

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.