The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

As an academic nurse practitioner hospitalist with faculty and leadership roles, I found that HM19 had many important and helpful topics that apply directly to my practice.

The “Onboarding Best Practices” session provided specific examples and tips for clinical ramp up, enculturation, and orienting staff to an academic career. As a result of this talk, I began the process of establishing a formal enculturation activity for new hires that includes a panel of senior advanced practice provider (APP) hospitalists to give career path advice.

The “Adaptive Leadership for Hospitalists” workshop provided the opportunity to practice emotional intelligence and effective communication in managing routine and difficult leadership interactions. The “Practice Models/Models of Care for Optimal Integration of NPs and PAs” presentation provided insight into variable team structures at other institutions that could be considered for improved efficiency in my group. The “Academic NP/PA” session provided ideas for how to apply for faculty positions in academic institutions. It also gave APPs who have faculty appointment specific illustrations of using current educational, quality improvement, and research projects to promote. I particularly found the “What Mentorship Has Meant to Me” talk significant. It gave practical essential advice on making sure there is chemistry and trust when seeking a mentor and staying engaged to be a successful mentee.

APPs, whether practicing in academic, private, or community settings, should attend the SHM Annual Conference. SHM is very inclusive and proud of APPs as colleagues and leaders. There are topics that directly apply to the needs of APP hospitalists – including career advancement – and that create excitement for APP practice in hospital medicine.

The Annual Conference also provides the very unique opportunity to meet and establish relationships with APP and physician colleagues and leaders nationwide. These relationships lend to career advancing opportunities for collaboration in clinical excellence, education, quality improvement, research, and leadership.
 

Dr. Apodaca is assistant professor and nurse practitioner hospitalist at the University of New Mexico. She is one of the first APPNP/PAs to receive faculty appointment at UNM. She serves as codirector of the UNM APP Hospital Medicine Fellowship and director of the APP Hospital Medicine Team. She is also the president of the New Mexico Chapter of SHM and is the first APP at her institution to achieve designation as a Fellow in Hospital Medicine.

As an academic nurse practitioner hospitalist with faculty and leadership roles, I found that HM19 had many important and helpful topics that apply directly to my practice.

The “Onboarding Best Practices” session provided specific examples and tips for clinical ramp up, enculturation, and orienting staff to an academic career. As a result of this talk, I began the process of establishing a formal enculturation activity for new hires that includes a panel of senior advanced practice provider (APP) hospitalists to give career path advice.

The “Adaptive Leadership for Hospitalists” workshop provided the opportunity to practice emotional intelligence and effective communication in managing routine and difficult leadership interactions. The “Practice Models/Models of Care for Optimal Integration of NPs and PAs” presentation provided insight into variable team structures at other institutions that could be considered for improved efficiency in my group. The “Academic NP/PA” session provided ideas for how to apply for faculty positions in academic institutions. It also gave APPs who have faculty appointment specific illustrations of using current educational, quality improvement, and research projects to promote. I particularly found the “What Mentorship Has Meant to Me” talk significant. It gave practical essential advice on making sure there is chemistry and trust when seeking a mentor and staying engaged to be a successful mentee.

APPs, whether practicing in academic, private, or community settings, should attend the SHM Annual Conference. SHM is very inclusive and proud of APPs as colleagues and leaders. There are topics that directly apply to the needs of APP hospitalists – including career advancement – and that create excitement for APP practice in hospital medicine.

The Annual Conference also provides the very unique opportunity to meet and establish relationships with APP and physician colleagues and leaders nationwide. These relationships lend to career advancing opportunities for collaboration in clinical excellence, education, quality improvement, research, and leadership.
 

Dr. Apodaca is assistant professor and nurse practitioner hospitalist at the University of New Mexico. She is one of the first APPNP/PAs to receive faculty appointment at UNM. She serves as codirector of the UNM APP Hospital Medicine Fellowship and director of the APP Hospital Medicine Team. She is also the president of the New Mexico Chapter of SHM and is the first APP at her institution to achieve designation as a Fellow in Hospital Medicine.

As an academic nurse practitioner hospitalist with faculty and leadership roles, I found that HM19 had many important and helpful topics that apply directly to my practice.

The “Onboarding Best Practices” session provided specific examples and tips for clinical ramp up, enculturation, and orienting staff to an academic career. As a result of this talk, I began the process of establishing a formal enculturation activity for new hires that includes a panel of senior advanced practice provider (APP) hospitalists to give career path advice.

The “Adaptive Leadership for Hospitalists” workshop provided the opportunity to practice emotional intelligence and effective communication in managing routine and difficult leadership interactions. The “Practice Models/Models of Care for Optimal Integration of NPs and PAs” presentation provided insight into variable team structures at other institutions that could be considered for improved efficiency in my group. The “Academic NP/PA” session provided ideas for how to apply for faculty positions in academic institutions. It also gave APPs who have faculty appointment specific illustrations of using current educational, quality improvement, and research projects to promote. I particularly found the “What Mentorship Has Meant to Me” talk significant. It gave practical essential advice on making sure there is chemistry and trust when seeking a mentor and staying engaged to be a successful mentee.

APPs, whether practicing in academic, private, or community settings, should attend the SHM Annual Conference. SHM is very inclusive and proud of APPs as colleagues and leaders. There are topics that directly apply to the needs of APP hospitalists – including career advancement – and that create excitement for APP practice in hospital medicine.

The Annual Conference also provides the very unique opportunity to meet and establish relationships with APP and physician colleagues and leaders nationwide. These relationships lend to career advancing opportunities for collaboration in clinical excellence, education, quality improvement, research, and leadership.
 

Dr. Apodaca is assistant professor and nurse practitioner hospitalist at the University of New Mexico. She is one of the first APPNP/PAs to receive faculty appointment at UNM. She serves as codirector of the UNM APP Hospital Medicine Fellowship and director of the APP Hospital Medicine Team. She is also the president of the New Mexico Chapter of SHM and is the first APP at her institution to achieve designation as a Fellow in Hospital Medicine.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Instructional video for fourth-degree obstetric laceration repair using modified beef tongue model

• The art of manipulation: Simplifying hysterectomy by preparing the learner

• Vaginal and bilateral thigh removal of a transobturator sling

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Instructional video for fourth-degree obstetric laceration repair using modified beef tongue model

• The art of manipulation: Simplifying hysterectomy by preparing the learner

• Vaginal and bilateral thigh removal of a transobturator sling

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Instructional video for fourth-degree obstetric laceration repair using modified beef tongue model

• The art of manipulation: Simplifying hysterectomy by preparing the learner

• Vaginal and bilateral thigh removal of a transobturator sling

Henry T. Lynch, MD, an eminent researcher and trailblazer in the field of hereditary cancers, died June 2, 2019, at age 91.

Born in 1928, Dr. Lynch joined the military at age 16, becoming a gunner in the U.S. Navy. After a stint as a professional boxer, he obtained his high school equivalent, then attended the University of Oklahoma as an undergraduate. After receiving his master’s degree from the University of Denver, he earned a PhD in human genetics from the University of Texas, Austin, and his medical degree from the University of Texas, Galveston.

In 1967, Dr. Lynch accepted a position at Creighton University, Omaha, Neb., where he would spend the rest of his career. He was the founder and director of the Hereditary Cancer Center at Creighton, served as chair of the institution’s Department of Preventive Medicine and Public Health, and was named the inaugural holder of the Charles F. and Mary C. Heider Endowed Chair in Cancer Research.

It was at Creighton that Dr. Lynch began his work on genetic causes of and familial susceptibility to certain cancers. Dr. Lynch created a hereditary cancer registry, and definitively identified several genetic cancer syndromes that persist through multiple familial generations.

Dr. Lynch is credited with identifying a strain of hereditary nonpolyposis colon cancer that was named after him – Lynch syndrome. He is also credited with the discovery of hereditary breast-ovarian cancer syndrome, which would eventually lead to the discovery of the BRCA gene.

Find the full remembrance on the ASCO website.

lfranki@mdedge.com

Henry T. Lynch, MD, an eminent researcher and trailblazer in the field of hereditary cancers, died June 2, 2019, at age 91.

Born in 1928, Dr. Lynch joined the military at age 16, becoming a gunner in the U.S. Navy. After a stint as a professional boxer, he obtained his high school equivalent, then attended the University of Oklahoma as an undergraduate. After receiving his master’s degree from the University of Denver, he earned a PhD in human genetics from the University of Texas, Austin, and his medical degree from the University of Texas, Galveston.

In 1967, Dr. Lynch accepted a position at Creighton University, Omaha, Neb., where he would spend the rest of his career. He was the founder and director of the Hereditary Cancer Center at Creighton, served as chair of the institution’s Department of Preventive Medicine and Public Health, and was named the inaugural holder of the Charles F. and Mary C. Heider Endowed Chair in Cancer Research.

It was at Creighton that Dr. Lynch began his work on genetic causes of and familial susceptibility to certain cancers. Dr. Lynch created a hereditary cancer registry, and definitively identified several genetic cancer syndromes that persist through multiple familial generations.

Dr. Lynch is credited with identifying a strain of hereditary nonpolyposis colon cancer that was named after him – Lynch syndrome. He is also credited with the discovery of hereditary breast-ovarian cancer syndrome, which would eventually lead to the discovery of the BRCA gene.

Find the full remembrance on the ASCO website.

lfranki@mdedge.com

Henry T. Lynch, MD, an eminent researcher and trailblazer in the field of hereditary cancers, died June 2, 2019, at age 91.

Born in 1928, Dr. Lynch joined the military at age 16, becoming a gunner in the U.S. Navy. After a stint as a professional boxer, he obtained his high school equivalent, then attended the University of Oklahoma as an undergraduate. After receiving his master’s degree from the University of Denver, he earned a PhD in human genetics from the University of Texas, Austin, and his medical degree from the University of Texas, Galveston.

In 1967, Dr. Lynch accepted a position at Creighton University, Omaha, Neb., where he would spend the rest of his career. He was the founder and director of the Hereditary Cancer Center at Creighton, served as chair of the institution’s Department of Preventive Medicine and Public Health, and was named the inaugural holder of the Charles F. and Mary C. Heider Endowed Chair in Cancer Research.

It was at Creighton that Dr. Lynch began his work on genetic causes of and familial susceptibility to certain cancers. Dr. Lynch created a hereditary cancer registry, and definitively identified several genetic cancer syndromes that persist through multiple familial generations.

Dr. Lynch is credited with identifying a strain of hereditary nonpolyposis colon cancer that was named after him – Lynch syndrome. He is also credited with the discovery of hereditary breast-ovarian cancer syndrome, which would eventually lead to the discovery of the BRCA gene.

Find the full remembrance on the ASCO website.

lfranki@mdedge.com

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – New data suggest pembrolizumab can increase 5-year overall survival (OS) for patients with advanced non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

In the phase 1b KEYNOTE-001 trial, the 5-year OS rate was 23.2% in treatment-naive patients and 15.5% in previously treated patients. This is in comparison to the 5.5% average 5-year OS rate observed in NSCLC patients who receive standard chemotherapy (Noone AM et al. SEER Cancer Statistics Review, 1975-2015).

“In total, the data confirm that pembrolizumab has the potential to improve long-term outcomes for both treatment-naive and previously treated patients with advanced non–small cell lung cancer,” said Edward B. Garon, MD, of the University of California, Los Angeles.

Dr. Garon and colleagues presented these results in a poster at the annual meeting of the American Society for Clinical Oncology, and the data were simultaneously published in the Journal of Clinical Oncology.

KEYNOTE-001 (NCT01295827) enrolled 550 patients with advanced NSCLC who had received no prior therapy (n = 101) or at least one prior line of therapy (n = 449). Initially, patients received pembrolizumab at varying doses depending on body weight, but the protocol was changed to a single dose of pembrolizumab at 200 mg every 3 weeks.

At a median follow-up of 60.6 months, 100 patients were still alive. Sixty patients had received at least 2 years of pembrolizumab, 14 of whom were treatment-naive at baseline, and 46 of whom were previously treated at baseline.

Five-year OS rates were best among patients who had high PD-L1 expression, which was defined as 50% or greater.

Among treatment-naive patients, the 5-year OS rate was 29.6% in PD-L1–high patients and 15.7% in PD-L1–low patients (expression of 1% to 49%). The median OS was 35.4 months and 19.5 months, respectively.

Among previously treated patients, the 5-year OS rate was 25.0% in PD-L1–high patients, 12.6% in patients with PD-L1 expression of 1%-49%, and 3.5% in patients with PD-L1 expression less than 1%. The median OS was 15.4 months, 8.5 months, and 8.6 months, respectively.

Among patients who received at least 2 years of pembrolizumab, the 5-year OS rate was 78.6% in the treatment-naive group and 75.8% in the previously treated group. The objective response rate was 86% and 91%, respectively. The rate of ongoing response at the data cutoff was 58% and 71%, respectively.

“The safety data did not show any unanticipated late toxicity, which I consider encouraging,” Dr. Garon noted.

He said rates of immune-mediated adverse events were similar at 3 years and 5 years of follow-up. At 5 years, 17% of patients (n = 92) had experienced an immune-related adverse event, the most common of which were hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%).

Dr. Garon disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis. KEYNOTE-001 was sponsored by Merck Sharp & Dohme Corp.

jensmith@mdedge.com

SOURCES: Garon E. et al. ASCO 2019, Abstract LBA9015; J Clin Oncol. 2019 June 2. doi: 10.1200/JCO.19.00934
 

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.

Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.

While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.

“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.

The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.

While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.

In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.

The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.

Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.

The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.

The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).

However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.

“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.

Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.

SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.

For Matthew Tuck, MD, MEd, FACP, associate section chief for hospital medicine at the Veterans Affairs Medical Center (VAMC) in Washington, leadership is something that hospitalists can and should be learning at every opportunity.

Some of the best insights about effective leadership, teamwork, and process improvement come from the business world and have been slower to infiltrate into hospital settings and hospitalist groups, he says. But Dr. Tuck has tried to take advantage of numerous opportunities for leadership development in his own career.

He has been a hospitalist since 2010 and is part of a group of 13 physicians, all of whom carry clinical, teaching, and research responsibilities while pursuing a variety of education, quality improvement, and performance improvement topics.

“My chair has been generous about giving me time to do teaching and research and to pursue opportunities for career development,” he said. The Washington VAMC works with four affiliate medical schools in the area, and its six daily hospital medicine services are all 100% teaching services with assigned residents and interns.

Dr. Tuck divides his professional time roughly one-third each between clinical – seeing patients 5 months a year on a consultative or inpatient basis with resident teams; administrative in a variety of roles; and research. He has academic appointments at the George Washington University (GWU) School of Medicine and at the Uniformed Services University of Health Sciences in Bethesda, Md. He developed the coursework for teaching evidence-based medicine to first- and second-year medical students at GWU.

He is also part of a large research consortium with five sites and $7.5 million in funding over 5 years from NIH’s National Institute on Minority Health and Health Disparities to study how genetic information from African American patients can predict their response to cardiovascular medications. He serves as the study’s site Principal Investigator at the VAMC.

Opportunities to advance his leadership skills have included the VA’s Aspiring Leaders Program and Leadership Development Mentoring Program, which teach leadership skills on topical subjects such as teaching, communications skills, and finance. The Master Teacher Leadership Development Program for medical faculty at GWU, where he attended medical school and did his internship and residency, offers six intensive, classroom-based 8-week courses over a 1-year period. They cover various topical subjects with faculty from the business world teaching principles of leadership. The program includes a mentoring action plan for participants and leads to a graduate certificate in leadership development from GWU’s Graduate School of Education and Human Development at the end of the year’s studies.

Dr. Tuck credits completing this kind of coursework for his current position of leadership in the VA and he tries to share what he has learned with the medical students he teaches.

“When I was starting out as a physician, I never received training in how to lead a team. I found myself trying to get everything done for my patients while teaching my learners, and I really struggled for the first couple of years to manage these competing demands on my time,” he said.

Now, on the first day of a new clinical rotation, he meets one-on-one with his residents to set out goals and expectations. “I say: ‘This is how I want rounds to be run. What are your expectations?’ That way we make sure we’re collaborating as a team. I don’t know that medical school prepares you for this kind of teamwork. Unless you bring a background in business, you can really struggle.”
 

Interest in hospital medicine

“Throughout our medical training we do a variety of rotations and clerkships. I found myself falling in love with all of them – surgery, psychiatry, obstetrics, and gynecology,” Dr. Tuck explained, as he reflected on how he ended up in hospital medicine. “As someone who was interested in all of these different fields of medicine, I considered myself a true medical generalist. And in hospitalized patients, who struggle with all of the different issues that bring them to the hospital, I saw a compilation of all my experiences in residency training combined in one setting.”

Hospital medicine was a relatively young field at that time, with few academic hospitalists, he said. “But I had good mentors who encouraged me to pursue my educational, research, and administrative interests. My affinity for the VA was also largely due to my training. We worked in multiple settings – academic, community-based, National Institutes of Health, and at the VA.”

Dr. Tuck said that, of all the settings in which he practiced, he felt the VA truly trained him best to be a doctor. “The experience made me feel like a holistic practitioner,” he said. “The system allowed me to take the best care of my patients, since I didn’t have to worry about whether I could make needed referrals to specialists. Very early in my internship year we were seeing very sick patients with multiple comorbidities, but it was easy to get a social worker or case manager involved, compared to other settings, which can be more difficult to navigate.”

While the VA is a “great health system,” Dr. Tuck said, the challenge is learning how to work with its bureaucracy. “If you don’t know how the system works, it can seem to get in your way.” But overall, he said, the VA functions well and compares favorably with private sector hospitals and health systems. That was also the conclusion of a recent study in the Journal of General Internal Medicine, which compared the quality of outpatient and inpatient care in VA and non-VA settings using recent performance measure data.¹ The authors concluded that the VA system performed similarly or better than non-VA health care on most nationally recognized measures of inpatient and outpatient care quality, although there is wide variation between VA facilities.
 

Working with the team

Another major interest for Dr. Tuck is team-based learning, which also grew out of his GWU leadership certificate course work on teaching teams and team development. He is working on a draft paper for publication with coauthor Patrick Rendon, MD, associate program director for the University of New Mexico’s internal medicine residency program, building on the group development stage theory – “Forming/Storming/Norming/Performing” – developed by Tuckman and Jenson.²

The theory offers 12 tips for optimizing inpatient ward team performance, such as getting the learners to buy in at an early stage of a project. “Everyone I talk to about our research is eager to learn how to apply these principles. I don’t think we’re unique at this center. We’re constantly rotating learners through the program. If you apply these principles, you can get learners to be more efficient starting from the first day,” he said.

The current inpatient team model at the Washington VAMC involves a broadly representative team from nursing, case management, social work, the business office, medical coding, utilization management, and administration that convenes every morning to discuss patient navigation and difficult discharges. “Everyone sits around a big table, and the six hospital medicine teams rotate through every fifteen minutes to review their patients’ admitting diagnoses, barriers to discharge and plans of care.”

At the patient’s bedside, a Focused Interdisciplinary Team (FIT) model, which Dr. Tuck helped to implement, incorporates a four-step process with clearly defined roles for the attending, nurse, pharmacist, and case manager or social worker. “Since implementation, our data show overall reductions in lengths of stay,” he said.

Dr. Tuck urges other hospitalists to pursue opportunities available to them to develop their leadership skills. “Look to your professional societies such as the Society of General Internal Medicine (SGIM) or SHM.” For example, SGIM’s Academic Hospitalist Commission, which he cochairs, provides a voice on the national stage for academic hospitalists and cosponsors with SHM an annual Academic Hospitalist Academy to support career development for junior academic hospitalists as educational leaders. Since 2016, its Distinguished Professor of Hospital Medicine recognizes a professor of hospital medicine to give a plenary address at the SGIM national meeting.

SGIM’s SCHOLAR Project, a subgroup of its Academic Hospitalist Commission, has worked to identify features of successful academic hospitalist programs, with the results published in the Journal of Hospital Medicine.³

“We learned that what sets successful programs apart is their leadership – as well as protected time for scholarly pursuits,” he said. “We’re all leaders in this field, whether we view ourselves that way or not.”

References

1. Price RA et al. Comparing quality of care in Veterans Affairs and Non–Veterans Affairs settings. J Gen Intern Med. 2018 Oct;33(10):1631-38.

2. Tuckman B, Jensen M. Stages of small group development revisited. Group and Organizational Studies. 1977;2:419-427.

3. Seymann GB et al. Features of successful academic hospitalist programs: Insights from the SCHOLAR (Successful hospitalists in academics and research) project. J Hosp Med. 2016 Oct;11(10):708-13.

For Matthew Tuck, MD, MEd, FACP, associate section chief for hospital medicine at the Veterans Affairs Medical Center (VAMC) in Washington, leadership is something that hospitalists can and should be learning at every opportunity.

Some of the best insights about effective leadership, teamwork, and process improvement come from the business world and have been slower to infiltrate into hospital settings and hospitalist groups, he says. But Dr. Tuck has tried to take advantage of numerous opportunities for leadership development in his own career.

He has been a hospitalist since 2010 and is part of a group of 13 physicians, all of whom carry clinical, teaching, and research responsibilities while pursuing a variety of education, quality improvement, and performance improvement topics.

“My chair has been generous about giving me time to do teaching and research and to pursue opportunities for career development,” he said. The Washington VAMC works with four affiliate medical schools in the area, and its six daily hospital medicine services are all 100% teaching services with assigned residents and interns.

Dr. Tuck divides his professional time roughly one-third each between clinical – seeing patients 5 months a year on a consultative or inpatient basis with resident teams; administrative in a variety of roles; and research. He has academic appointments at the George Washington University (GWU) School of Medicine and at the Uniformed Services University of Health Sciences in Bethesda, Md. He developed the coursework for teaching evidence-based medicine to first- and second-year medical students at GWU.

He is also part of a large research consortium with five sites and $7.5 million in funding over 5 years from NIH’s National Institute on Minority Health and Health Disparities to study how genetic information from African American patients can predict their response to cardiovascular medications. He serves as the study’s site Principal Investigator at the VAMC.

Opportunities to advance his leadership skills have included the VA’s Aspiring Leaders Program and Leadership Development Mentoring Program, which teach leadership skills on topical subjects such as teaching, communications skills, and finance. The Master Teacher Leadership Development Program for medical faculty at GWU, where he attended medical school and did his internship and residency, offers six intensive, classroom-based 8-week courses over a 1-year period. They cover various topical subjects with faculty from the business world teaching principles of leadership. The program includes a mentoring action plan for participants and leads to a graduate certificate in leadership development from GWU’s Graduate School of Education and Human Development at the end of the year’s studies.

Dr. Tuck credits completing this kind of coursework for his current position of leadership in the VA and he tries to share what he has learned with the medical students he teaches.

“When I was starting out as a physician, I never received training in how to lead a team. I found myself trying to get everything done for my patients while teaching my learners, and I really struggled for the first couple of years to manage these competing demands on my time,” he said.

Now, on the first day of a new clinical rotation, he meets one-on-one with his residents to set out goals and expectations. “I say: ‘This is how I want rounds to be run. What are your expectations?’ That way we make sure we’re collaborating as a team. I don’t know that medical school prepares you for this kind of teamwork. Unless you bring a background in business, you can really struggle.”
 

Interest in hospital medicine

“Throughout our medical training we do a variety of rotations and clerkships. I found myself falling in love with all of them – surgery, psychiatry, obstetrics, and gynecology,” Dr. Tuck explained, as he reflected on how he ended up in hospital medicine. “As someone who was interested in all of these different fields of medicine, I considered myself a true medical generalist. And in hospitalized patients, who struggle with all of the different issues that bring them to the hospital, I saw a compilation of all my experiences in residency training combined in one setting.”

Hospital medicine was a relatively young field at that time, with few academic hospitalists, he said. “But I had good mentors who encouraged me to pursue my educational, research, and administrative interests. My affinity for the VA was also largely due to my training. We worked in multiple settings – academic, community-based, National Institutes of Health, and at the VA.”

Dr. Tuck said that, of all the settings in which he practiced, he felt the VA truly trained him best to be a doctor. “The experience made me feel like a holistic practitioner,” he said. “The system allowed me to take the best care of my patients, since I didn’t have to worry about whether I could make needed referrals to specialists. Very early in my internship year we were seeing very sick patients with multiple comorbidities, but it was easy to get a social worker or case manager involved, compared to other settings, which can be more difficult to navigate.”

While the VA is a “great health system,” Dr. Tuck said, the challenge is learning how to work with its bureaucracy. “If you don’t know how the system works, it can seem to get in your way.” But overall, he said, the VA functions well and compares favorably with private sector hospitals and health systems. That was also the conclusion of a recent study in the Journal of General Internal Medicine, which compared the quality of outpatient and inpatient care in VA and non-VA settings using recent performance measure data.¹ The authors concluded that the VA system performed similarly or better than non-VA health care on most nationally recognized measures of inpatient and outpatient care quality, although there is wide variation between VA facilities.
 

Working with the team

Another major interest for Dr. Tuck is team-based learning, which also grew out of his GWU leadership certificate course work on teaching teams and team development. He is working on a draft paper for publication with coauthor Patrick Rendon, MD, associate program director for the University of New Mexico’s internal medicine residency program, building on the group development stage theory – “Forming/Storming/Norming/Performing” – developed by Tuckman and Jenson.²

The theory offers 12 tips for optimizing inpatient ward team performance, such as getting the learners to buy in at an early stage of a project. “Everyone I talk to about our research is eager to learn how to apply these principles. I don’t think we’re unique at this center. We’re constantly rotating learners through the program. If you apply these principles, you can get learners to be more efficient starting from the first day,” he said.

The current inpatient team model at the Washington VAMC involves a broadly representative team from nursing, case management, social work, the business office, medical coding, utilization management, and administration that convenes every morning to discuss patient navigation and difficult discharges. “Everyone sits around a big table, and the six hospital medicine teams rotate through every fifteen minutes to review their patients’ admitting diagnoses, barriers to discharge and plans of care.”

At the patient’s bedside, a Focused Interdisciplinary Team (FIT) model, which Dr. Tuck helped to implement, incorporates a four-step process with clearly defined roles for the attending, nurse, pharmacist, and case manager or social worker. “Since implementation, our data show overall reductions in lengths of stay,” he said.

Dr. Tuck urges other hospitalists to pursue opportunities available to them to develop their leadership skills. “Look to your professional societies such as the Society of General Internal Medicine (SGIM) or SHM.” For example, SGIM’s Academic Hospitalist Commission, which he cochairs, provides a voice on the national stage for academic hospitalists and cosponsors with SHM an annual Academic Hospitalist Academy to support career development for junior academic hospitalists as educational leaders. Since 2016, its Distinguished Professor of Hospital Medicine recognizes a professor of hospital medicine to give a plenary address at the SGIM national meeting.

SGIM’s SCHOLAR Project, a subgroup of its Academic Hospitalist Commission, has worked to identify features of successful academic hospitalist programs, with the results published in the Journal of Hospital Medicine.³

“We learned that what sets successful programs apart is their leadership – as well as protected time for scholarly pursuits,” he said. “We’re all leaders in this field, whether we view ourselves that way or not.”

References

1. Price RA et al. Comparing quality of care in Veterans Affairs and Non–Veterans Affairs settings. J Gen Intern Med. 2018 Oct;33(10):1631-38.

2. Tuckman B, Jensen M. Stages of small group development revisited. Group and Organizational Studies. 1977;2:419-427.

3. Seymann GB et al. Features of successful academic hospitalist programs: Insights from the SCHOLAR (Successful hospitalists in academics and research) project. J Hosp Med. 2016 Oct;11(10):708-13.

For Matthew Tuck, MD, MEd, FACP, associate section chief for hospital medicine at the Veterans Affairs Medical Center (VAMC) in Washington, leadership is something that hospitalists can and should be learning at every opportunity.

Some of the best insights about effective leadership, teamwork, and process improvement come from the business world and have been slower to infiltrate into hospital settings and hospitalist groups, he says. But Dr. Tuck has tried to take advantage of numerous opportunities for leadership development in his own career.

He has been a hospitalist since 2010 and is part of a group of 13 physicians, all of whom carry clinical, teaching, and research responsibilities while pursuing a variety of education, quality improvement, and performance improvement topics.

“My chair has been generous about giving me time to do teaching and research and to pursue opportunities for career development,” he said. The Washington VAMC works with four affiliate medical schools in the area, and its six daily hospital medicine services are all 100% teaching services with assigned residents and interns.

Dr. Tuck divides his professional time roughly one-third each between clinical – seeing patients 5 months a year on a consultative or inpatient basis with resident teams; administrative in a variety of roles; and research. He has academic appointments at the George Washington University (GWU) School of Medicine and at the Uniformed Services University of Health Sciences in Bethesda, Md. He developed the coursework for teaching evidence-based medicine to first- and second-year medical students at GWU.

He is also part of a large research consortium with five sites and $7.5 million in funding over 5 years from NIH’s National Institute on Minority Health and Health Disparities to study how genetic information from African American patients can predict their response to cardiovascular medications. He serves as the study’s site Principal Investigator at the VAMC.

Opportunities to advance his leadership skills have included the VA’s Aspiring Leaders Program and Leadership Development Mentoring Program, which teach leadership skills on topical subjects such as teaching, communications skills, and finance. The Master Teacher Leadership Development Program for medical faculty at GWU, where he attended medical school and did his internship and residency, offers six intensive, classroom-based 8-week courses over a 1-year period. They cover various topical subjects with faculty from the business world teaching principles of leadership. The program includes a mentoring action plan for participants and leads to a graduate certificate in leadership development from GWU’s Graduate School of Education and Human Development at the end of the year’s studies.

Dr. Tuck credits completing this kind of coursework for his current position of leadership in the VA and he tries to share what he has learned with the medical students he teaches.

“When I was starting out as a physician, I never received training in how to lead a team. I found myself trying to get everything done for my patients while teaching my learners, and I really struggled for the first couple of years to manage these competing demands on my time,” he said.

Now, on the first day of a new clinical rotation, he meets one-on-one with his residents to set out goals and expectations. “I say: ‘This is how I want rounds to be run. What are your expectations?’ That way we make sure we’re collaborating as a team. I don’t know that medical school prepares you for this kind of teamwork. Unless you bring a background in business, you can really struggle.”
 

Interest in hospital medicine

“Throughout our medical training we do a variety of rotations and clerkships. I found myself falling in love with all of them – surgery, psychiatry, obstetrics, and gynecology,” Dr. Tuck explained, as he reflected on how he ended up in hospital medicine. “As someone who was interested in all of these different fields of medicine, I considered myself a true medical generalist. And in hospitalized patients, who struggle with all of the different issues that bring them to the hospital, I saw a compilation of all my experiences in residency training combined in one setting.”

Hospital medicine was a relatively young field at that time, with few academic hospitalists, he said. “But I had good mentors who encouraged me to pursue my educational, research, and administrative interests. My affinity for the VA was also largely due to my training. We worked in multiple settings – academic, community-based, National Institutes of Health, and at the VA.”

Dr. Tuck said that, of all the settings in which he practiced, he felt the VA truly trained him best to be a doctor. “The experience made me feel like a holistic practitioner,” he said. “The system allowed me to take the best care of my patients, since I didn’t have to worry about whether I could make needed referrals to specialists. Very early in my internship year we were seeing very sick patients with multiple comorbidities, but it was easy to get a social worker or case manager involved, compared to other settings, which can be more difficult to navigate.”

While the VA is a “great health system,” Dr. Tuck said, the challenge is learning how to work with its bureaucracy. “If you don’t know how the system works, it can seem to get in your way.” But overall, he said, the VA functions well and compares favorably with private sector hospitals and health systems. That was also the conclusion of a recent study in the Journal of General Internal Medicine, which compared the quality of outpatient and inpatient care in VA and non-VA settings using recent performance measure data.¹ The authors concluded that the VA system performed similarly or better than non-VA health care on most nationally recognized measures of inpatient and outpatient care quality, although there is wide variation between VA facilities.
 

Working with the team

Another major interest for Dr. Tuck is team-based learning, which also grew out of his GWU leadership certificate course work on teaching teams and team development. He is working on a draft paper for publication with coauthor Patrick Rendon, MD, associate program director for the University of New Mexico’s internal medicine residency program, building on the group development stage theory – “Forming/Storming/Norming/Performing” – developed by Tuckman and Jenson.²

The theory offers 12 tips for optimizing inpatient ward team performance, such as getting the learners to buy in at an early stage of a project. “Everyone I talk to about our research is eager to learn how to apply these principles. I don’t think we’re unique at this center. We’re constantly rotating learners through the program. If you apply these principles, you can get learners to be more efficient starting from the first day,” he said.

The current inpatient team model at the Washington VAMC involves a broadly representative team from nursing, case management, social work, the business office, medical coding, utilization management, and administration that convenes every morning to discuss patient navigation and difficult discharges. “Everyone sits around a big table, and the six hospital medicine teams rotate through every fifteen minutes to review their patients’ admitting diagnoses, barriers to discharge and plans of care.”

At the patient’s bedside, a Focused Interdisciplinary Team (FIT) model, which Dr. Tuck helped to implement, incorporates a four-step process with clearly defined roles for the attending, nurse, pharmacist, and case manager or social worker. “Since implementation, our data show overall reductions in lengths of stay,” he said.

Dr. Tuck urges other hospitalists to pursue opportunities available to them to develop their leadership skills. “Look to your professional societies such as the Society of General Internal Medicine (SGIM) or SHM.” For example, SGIM’s Academic Hospitalist Commission, which he cochairs, provides a voice on the national stage for academic hospitalists and cosponsors with SHM an annual Academic Hospitalist Academy to support career development for junior academic hospitalists as educational leaders. Since 2016, its Distinguished Professor of Hospital Medicine recognizes a professor of hospital medicine to give a plenary address at the SGIM national meeting.

SGIM’s SCHOLAR Project, a subgroup of its Academic Hospitalist Commission, has worked to identify features of successful academic hospitalist programs, with the results published in the Journal of Hospital Medicine.³

“We learned that what sets successful programs apart is their leadership – as well as protected time for scholarly pursuits,” he said. “We’re all leaders in this field, whether we view ourselves that way or not.”

References

1. Price RA et al. Comparing quality of care in Veterans Affairs and Non–Veterans Affairs settings. J Gen Intern Med. 2018 Oct;33(10):1631-38.

2. Tuckman B, Jensen M. Stages of small group development revisited. Group and Organizational Studies. 1977;2:419-427.

3. Seymann GB et al. Features of successful academic hospitalist programs: Insights from the SCHOLAR (Successful hospitalists in academics and research) project. J Hosp Med. 2016 Oct;11(10):708-13.

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.


 

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.


 

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.